Tsunade

is a descendant of the Senju and Uzumaki Clan along with one of Konohagakure's Sannin; famed as the world's strongest kunoichi and its greatest medical-nin. The repeated loss of her loved ones caused Tsunade to develop a crippling fear of blood and she would later abandon the life of a shinobi for many years. She is eventually persuaded to return to Konoha and take on the mantle of, where her skills prove invaluable to the village.

Background
Tsunade is the granddaughter of Hashirama Senju and Mito Uzumaki. Because Hashirama was the First Hokage of Konohagakure, Tsunade is called. Hashirama doted on Tsunade when she was very young because she was his first grandchild, and found her deviance and her adoption of his own gambling habits highly amusing; Tsunade inherited his necklace when he died. After she graduated from Konoha's Academy, Tsunade was teamed with Orochimaru and Jiraiya under the leadership of Hiruzen Sarutobi. When Jiraya failed to acquire a bell during the team's first bell test, Tsunade teased him, prompting him to criticise her flat chest. Despite this remark, Jiraiya had a certain interest in Tsunade from their first meeting, which only increased after her breasts developed; when she nearly killed him for spying on her while she bathed, he was forced to be more discrete about his interests.

Tsunade's younger brother, Nawaki dreamed of someday becoming Hokage so that he could protect Konoha, their grandfather's legacy. On Nawaki's twelfth birthday, Tsunade kissed his forehead and gave him Hashirama's necklace in the hopes that it would help him achieve his dream. He died the next day, a casualty of the ongoing Second Shinobi World War, thus returning the necklace to her. Tsunade began advocating for the inclusion of medical-nin on all four-man squads in order to avoid future deaths like Nawaki's. Hiruzen, the Third Hokage, agreed with her arguments, but could not dedicate resources to the necessary implementation due to the ongoing war. Dan Katō, on the other hand, shared her views, and as their relationship developed he confided with her his dreams of becoming Hokage so that he could bring change to Konoha and protect his loved one from death. Tsunade kissed his forehead and gave him Hashirama's necklace in the hopes that it would help him achieve his dream.

Although their team under Hiruzen's leadership had disbanded, Tsunade, Orochimaru, and Jiraiya continued fighting together during the Second Shinobi World War. During one such fight in Amegakure, they were the only three to survive an encounter with Hanzō, for which accomplishment Hanzō dubbed them Konoha's "Legendary Sannin". In the aftermath of the battle, Jiraiya opted not to return to Konoha so that he could train the Ame orphans. Tsunade would go on to make her own independent contributions to the war, frequently counteracting Chiyo of Sunagakure's poisons. Although Tsunade's actions are said to have won the war for Konoha, Tsunade was unable to prevent Dan's death, and her failure to stop his severe blood loss caused her to develop haemophobia.

With Dan's death, Hashirama's necklace returned to Tsunade once again, convincing some that the necklace was cursed to kill anyone who wore it other than Tsunade. Tsunade herself became convinced that achieving one's dreams was impossible and that to be Hokage was a fool's job. She therefore left Konoha, taking Dan's niece, Shizune, with her to train her as an apprentice. Due to her blood phobia, Tsunade retired from any direct involvement in medicine or combat, instead relying on Shizune whenever a need for either came up.

Personality
Tsunade was very willing to believe in the attainability of dreams while Nawaki and Dan were alive, and that by supporting and encouraging those dreams she might be able to help achieve them. When both died gruesomely shortly after receiving her support, Tsunade lost faith in the idea of dreaming for anything, believing that the mere pursuit would be doomed from the outset. She becomes especially critical of wanting to be Hokage, as both Dan and Nawaki died trying to attain the title and the past Hokage have all died prematurely and, Tsunade argues, pointlessly because they held the position; she concludes that to be Hokage is a fool's job.

Tsunade is forced to reconsider her cynicism upon meeting Naruto Uzumaki, who demonstrates two things to her: just because a goal seems impossible does not mean it actually is, as Naruto is able to master the Rasengan unprecedentedly quickly despite seemingly lacking any natural talent; just because the dreamer dies does not mean the dream itself does, as Nawaki and Dan's desire to become Hokage lives on in Naruto. Because Naruto is so very much an exception to how she thought the world worked, Tsunade puts her faith in dreams once again, a desire so strong that she overcomes her fear of blood. She becomes Hokage herself, partly so that she can live Nawaki and Dan's dream for them, but also so that she can pave the way for Naruto inevitably holding the title. Just as she once did, Tsunade supports all other dreams that she can: when Rock Lee tells her he dreams of being a ninja despite knowing he may die trying, she does not argue his decision and, in the anime, does all that she can to ensure he survives.

As Hokage, Tsunade is committed to protecting Konoha and its villagers, willing to give her life for her village and allies if necessary. She does this because Nawaki and Dan loved Konoha and so she keeps their dreams alive by doing so, but also because Konoha's continued survival honours all those who gave their lives creating it and keeping it safe. Although her reasons are somewhat different, the outcome is nevertheless consistent with the Will of Fire. Tsunade is similarly optimistic about the next generation of Konoha's ninja, especially Naruto, convinced that the village's future will be in good hands because of them. She in fact becomes angry when others lack this same faith in Naruto and his peers, believing it is better to let them try and then fail than to assume their failure is inevitable and thus prevent them from trying. Demonstrations of her own faith include: congratulating Shikamaru Nara for his failed mission because at least none of his teammates died; not labelling Sasuke Uchiha a missing-nin because she trusts that Naruto can someday convince him to return to Konoha.

Despite her many noble qualities, Tsunade is not without her faults. She is blunt and short-tempered, prone to striking Naruto for his immaturity or Jiraiya for his perversion; she is widely feared because of this tendency. Her own behaviour isn't much better than theirs, as she drinks constantly, sometimes sleeps on the job, and tries as much as she can to have other people do her work for her. One of her favourite vices is gambling, which she acquired from her grandfather, Hashirama Senju. Despite how often and how irresponsibly she gambles, Tsunade has notoriously bad luck, causing those who have made huge profits off of her to call her. Tsunade is fully aware of how unlucky she is, and so whenever she hits a winning streak she takes it as a bad omen and prepares for the worst; she has at times tried using her bad luck to her advantage, betting on outcomes she doesn't want so that her unluckiness will prevent them from happening. Hashirama finds Tsunade's many bad habits highly amusing on a personal level, but when he is told that Tsunade is Hokage he immediately worries about what misfortunes she's brought upon Konoha.

Jiraiya assumed that there was a mutual attraction between him and Tsunade from their first meeting, a statement that only served to annoy and anger her. Despite his many advances over the years, Tsunade never reciprocated his feelings, only ever loving Dan, even decades after his death. Jiraiya wasn't discouraged by this and claimed that her repeated rejections had not only made him stronger, but they've been excellent material for his Icha Icha series of books. Though he concluded that to be happy wasn't his fate. Tsunade doubted he believed his own words and she commented that he did not need to put on a brave front when he returned from Amegakure. When Jiraiya ended up dying during that same mission, Tsunade privately mourned for the loss of her dear friend and team-mate. Her greatest desire was to be with her lost loved ones, while supporting Dan as he lived out his dream of being Hokage. Despite this, she chose not to have Dan and Nawaki reincarnated when given the chance as she realised it would go against everything they stood for.

Despite Orochimaru's contribution in their victory in the Fourth Shinobi World War, Tsunade remains guarded against him due to a long history of distrust. This influenced her thoughts of anyone related to him, and she was furious at Naruto, in his capacity as the Seventh Hokage, for allowing Orochimaru's child, Mitsuki, to immigrate into Konohagakure. Mitsuki's heritage alone led Tsunade to develop a prejudiced view that he is as dangerous as his parent.

Appearance
Tsunade is a fair-skinned woman with brown eyes and straight blonde hair that parts above her forehead. Her hair has shoulder-length bangs that frame her face and the rest reaches her lower-back. While as a child through her young-adult years she wore her hair in a high ponytail, she later keeps it tied in two loose ponytails. The Strength of a Hundred Seal - taking the appearance of a violet diamond shape - is clearly visible on her forehead. In her childhood, she wore grey mesh shirt and over it a teal-colored kimino with short sleeves and red-lining around the collars which she secured with a blue sash. She also wore red wristbands and white wrapping over her calves with blue sandals.

She was very skinny throughout her childhood to the point of being known as flat-chested. By young-adulthood however, Tsunade grew into a slender woman of curvaceous frame with above-average height and noticeably large breasts, which Jiraiya noted to be 106 centimetres; she is in fact widely regarded as the most beautiful kunoichi in the world. By her fifties, she appears much older, being heavily wrinkled while rather frail-looking (presumably from over-usage of her Creation Rebirth). However, Tsunade maintains her youthful appearance using a unique Transformation Technique. Tsunade often wears a grass-green haori with the kanji for on the back, inside a red circle. Underneath she wears a grey, kimono-style blouse with no sleeves, held closed by a broad, dark bluish-grey obi that matches her pants. Her blouse is closed quite low, revealing her sizeable cleavage. She wears open-toed, strappy black sandals with high heels. She has red nail polish on both her fingernails and toenails and uses a soft pink lipstick. She wears the First Hokage's necklace for many years until she gives it to Naruto.

Abilities
Like other students of the Third Hokage, Tsunade is an exceptionally talented shinobi. Her skills became well known following the Second Shinobi World War when dubbed by Hanzō as a Sannin, alongside Jiraiya and Orochimaru. Tsunade's skills are popularly held as the reason for Konoha's victory during that war, and in the years following, became known as the world's strongest kunoichi. Despite being rusty, Tsunade's skills easily outclassed Kabuto Yakushi's when they battled, with him having to rely on using a Military Rations Pill to continue battling, and use her fear of blood against her to gain the upper hand. Upon overcoming this, she fought Orochimaru one on one and defeated him near single-handedly. She would later go on to become Konoha's Fifth Hokage, and was responsible for saving countless villagers when Pain decimated the village in Part II. Even the likes of Madara Uchiha admits that Tsunade was worthy of being a Kage.

Chakra Control and Physical Prowess
As a descendant of both the Senju and Uzumaki Clans, Tsunade inherited their life force and chakra, enabling her to battle the likes of Madara Uchiha for over half a day without even getting exhausted, then having enough chakra to heal several thousand shinobi during the final battle with Obito Uchiha. She also has excellent control over her chakra, a necessary prerequisite to her job as a medical-nin. After the Second Shinobi World War, she started gradually storing her chakra into the Strength of a Hundred Seal on her forehead. When the seal is released, Tsunade has access to all the accumulated chakra, totaling a so-named hundred-times her usual chakra levels. Although she normally uses this extra chakra to heal injuries or perform her other jutsu, she can also transfer the chakra to others, either to replenish or amplify their own.

Tsunade teaches her student, Sakura Haruno, how to build up chakra in her fists and release it on contact with a target, causing severe damage. Tsunade presumably uses this ability herself, but it isn't always clear when since she is naturally very strong, enough to lift Gamabunta's sword. Her physical accomplishments, whatever the cause, include: splitting the ground with only a finger, breaking six of Jiraiya's ribs, both his arms, and rupturing several of his internal organs. She has even broke through Susanoo, an "absolute defense", with only a few hits.

Tsunade believes it is vital for a medical-nin to avoid injury, as they cannot perform their duties if anything happens to them. To a certain extent, her unnatural strength helps her in this regard, as opponents may avoid getting near her so that she cannot strike them. At the same time, though, Tsunade is regularly injured in combat, even going so far as to place herself in harm's way in order to protect her allies. This is all because Tsunade deems her Creation Rebirth ability a reasonable exception to the "avoid injury" tenet, as she can receive serious damage and still survive. Even without the Creation Rebirth, Tsunade's ability to endure injury is quite impressive, as she can survive several mortal stabs to the chest and remain able to perform jutsu after being bisected.

Ninjutsu
Tsunade can summon segments of Katsuyu, a slug from the Shikkotsu Forest. In addition to fighting alongside Tsunade, Katsuyu can use her divisions as a form of long-distance communication or to move and shield Tsunade's injured allies. By linking with Katsuyu, Tsunade can monitor those that Katsuyu has attached to, remotely healing them and replenishing their chakra as needed.

Tsunade's natures include Lightning, Fire, Water, and Earth, as well as Yang and in the anime Yin Release. She isn't seen directly using any of these natures in the series, although her Body Pathway Derangement is suggested to use some amount of lightning chakra: she injects her chakra into an opponent, scrambling their body's electric signals so that commands to move their hand instead move their leg, and so on.

In addition to her other skills, the anime shows Tsunade using some amount of space–time ninjutsu, fūinjutsu, and barrier ninjutsu.

Transformation Technique
Despite being in her fifties, Tsunade's Transformation Technique makes her appear as if she were still in her twenties. She readily alters what age she appears in order to avoid her gambling debts. Tsunade's unique transformation seems to be permanent, as she can maintain this form without exerting any effort, even while injured or asleep. The transformation dispels when she runs out of chakra, reverting her to her natural appearance.

Medical Ninjutsu
Tsunade is hailed as the world's greatest medical-nin, able to identify ailments at a glance and treat conditions that other medical-nin deem impossible to cure. Her skills are enough that Orochimaru believed she could reverse the necrosis-like effects of the Dead Demon Consuming Seal, heal the psychological damage of Tsukuyomi, fix the damage to Rock Lee's spine when he was deemed a helpless case and counteract the effects of the Three Coloured Pills with instructions from the Nara Clan Medical Encyclopaedia. Her medical prowess was again demonstrated was when she near-instantly healed Shikamaru’s severe chakra depletion after he came into contact with a root of the God Tree; the chakra cloak surrounding him noticeably reacting to her treatment.

Undoubtedly, the pinnacle of Tsunade's medical prowess is her Creation Rebirth, which draws on her vast chakra supplies to instantaneously heal any wounds she receives. Because it requires no hand seals to perform, she needs no conscious effort on her part once active, and can heal any damage no matter how severe (her chakra levels permitting); Orochimaru describes it as a form of immortality that even he is envious of. Despite how useful it is in battle, Creation Rebirth is a double-edged sword: the body's cells can only divide and be created a set amount of times, so whenever Tsunade uses the technique she shortens her lifespan. Because of this, she only uses it in very desperate situations.

Tsunade's skills extend beyond the typical medical ninjutsu. She earned fame during the Second Shinobi World War for being the only person able to make antidotes for the poisons of Sunagakure's Chiyo. Similarly, she can make sleeping potions that are undetectable to even the most skilled ninja. She is knowledgeable enough to perform autopsies and examine damage on a cellular level. Following the Fourth Shinobi World War, she studies the material that the White Zetsu Army is made of and learns to make prosthetic limbs from it. In the anime, she researches Kabuto Yakushi's Yin Healing Wound Destruction and uses what she finds to raise the survival rate of Rock Lee's medical procedure. Due to her vast medical knowledge, Tsunade was primarily responsible for setting up the modern system of medical-nin, though she exempts herself from many of the laws that govern them due to her Creation Rebirth.

Search for Tsunade
Tsunade hits a jackpot while playing the slot machines in Tanzaku Quarters. She takes this as a sign that something bad is about to happen and makes immediate plans to leave the city, but Shizune convinces her to visit a local castle before they go. While they're there, the castle is destroyed by a snake, Orochimaru's way of saying hello. Tsunade immediately notices the damage to his arms and, guessing he wants her to heal them, preemptively refuses. Orochimaru's assistant, Kabuto Yakushi, explains that they've tried all other options and that only Tsunade can help. She asks how his arms were damaged, to which Orochimaru responds that the damage was received while he killed Hiruzen Sarutobi. Tsunade becomes enraged and threatens to kill Orochimaru, but he piques her interest when he offers to revive Nawaki and Dan Katō.

Tsunade asks what he would do if his arms were restored. Orochimaru replies that he would destroy Konohagakure, which is what he was trying to do when his arms were damaged in the first place. Shizune tries to convince Tsunade to help her kill Orochimaru and Kabuto, but they decide to leave instead, giving Tsunade a week to decide. While having dinner later, they are found by Jiraiya. Jiraiya asks her to become the Fifth Hokage, which she refuses, upsetting Jiraiya's companion, Naruto Uzumaki. Tsunade recognises Naruto as the jinchūriki of the Nine-Tails and starts remarking on what a waste it was for the Fourth Hokage to give his life saving Konoha from the Nine-Tails. She reflects further that all the past Hokage have wasted their lives for the village and concludes that only a fool would ever want the title.

Naruto, who has his own dreams of being Hokage, is enraged and tries to attack Tsunade. Jiraiya holds him back, but Tsunade agrees to fight with him outside the restaurant. Tsunade easily outmatches Naruto using only one finger for offence and defence, but she's unsettled by how similar his resolve is to Nawaki and Dan's. While she's distracted by this, Naruto attacks her with an incomplete Rasengan, which she once again avoids using only a finger. She berates Jiraiya for teaching Naruto the Rasengan at all, declaring it cruel to let someone as untalented as him believe he can master something as complicated as the Rasengan. Naruto vows to complete it in three days, prompting Tsunade to make a wager: if Naruto can master the Rasengan in a week, she'll give him the First Hokage's necklace; if he can't, she gets his wallet. Naruto agrees.

Tsunade and Jiraiya have drinks later. Jiraiya guesses that Orochimaru made some offer to Tsunade. He doesn't ask for details about the offer, but he promises to personally kill her if she does anything to endanger Konoha. She claims not to care about the village, so Jiraiya reminds her of how important the village was to Nawaki and Dan; he further notes how similar they, particularly Nawaki, are to Naruto. Tsunade keeps tabs on Naruto as he trains, but by the end of the week he has failed to master the Rasengan and the intense training leaves him bedridden. Shizune pleads with Tsunade not to accept Orochimaru's deal and, when this fails, she tries to use force, prompting Tsunade to knock her out. She meets with Jiraiya again and drugs his drink, knocking him out and, when he wakes up the next morning, making it difficult for him to use his chakra.

Tsunade meets with Orochimaru and agrees to heal his arms on the condition that he would leave Konoha alone. Orochimaru agrees. She approaches him, apparently to heal him, but Kabuto notices at the last moment that she has killing intent and stops her. Orochimaru questions why she would deceive him, to which she replies that she knew he was lying about sparing Konoha. Although she desperately wants to see Nawaki and Dan again, she knows they wouldn't want to be brought back at the cost of Konoha's safety, something Naruto has reminded her of. Orochimaru and Kabuto state that they'll force her to heal his arms, causing her to attack them. They draw her away from the city and Kabuto, a medic-nin, tries neutralising her, but she heals all the debilitating damage he does. Unable to stop her through conventional means, Kabuto slits his own wrists and coats her with his blood, paralysing her due to her phobia.

Jiraiya, Shizune, and Naruto eventually arrive to help. Shizune looks after Tsunade as she shudders from the blood while Jiraiya fights Orochimaru and Naruto fights Kabuto. Naruto is quickly defeated by Kabuto, as is Shizune when she tries to face him afterwards. Kabuto approaches Tsunade and tries to restrain her, which she is unable to fend off in her condition. Naruto stops him and attacks with an incomplete Rasengan, but misses, causing Kabuto to start commenting on his lack of talent, just as Tsunade did the week before. Naruto persists and, after making a shadow clone to help him, he is able to strike Kabuto with a perfected Rasengan. Kabuto is defeated, but as his last act he severs Naruto's heart muscles. Tsunade tries healing him, fearing that he'll die just like Nawaki and Dan did. She succeeds, and in a brief moment of regained consciousnesses Naruto claims the necklace he's won.

Orochimaru decides to kill Naruto and attacks with his Sword of Kusanagi. Tsunade uses her body to block the attack, her way of protecting Naruto, Konoha's future Hokage. Orochimaru keeps trying to attack him, which Tsunade keeps using her body to block. Her resolve to protect Naruto eventually overcomes her fear of blood, allowing her to go on the offensive: she kicks Orochimaru, activates Creation Rebirth to heal all the damage she's received, and declares her acceptance of the position of Fifth Hokage. She, Jiraiya, and Orochimaru each summon Katsuyu, Gamabunta, and Manda, respectively. When Manda proves too elusive for Katsuyu and Gamabunta, Tsunade uses Gamabunta's sword to pin Manda to the ground with his mouth shut. She then delivers a sequence of punches to Orochimaru's face, forcing him to escape with Kabuto; before he leaves, he warns that he has other ways of fixing his arms.

Having used so much chakra during the fight, Tsunade's younger transformation fades after the battle, but it is restored before Naruto wakes up. When he hears about what happened while he was unconscious, Naruto expresses his concern that she isn't qualified to be Fifth Hokage, being vastly inferior to Hiruzen. Tsunade challenges him to a fight and once again outmatches him using a single finger. Rather than defeat him, however, she kisses his forehead to symbolise her faith in his achieving his dreams, just as she once did for Nawaki and Dan.

Sasuke Recovery Mission
When they get back to Konoha, the villagers start making preparations to officially place Tsunade into office. Before that can happen, Naruto has Tsunade heal the damage to the minds of Kakashi Hatake and Sasuke Uchiha. She also looks at the damage to Rock Lee's spine; although she's the only one who can fix it, she confesses that there's a fifty percent chance he wouldn't survive the procedure and recommends he give up on life as a ninja. After thinking it over, Lee tells her plainly that being a ninja is his dream, which she cannot argue with. In the anime, Tsunade tries to improve his chances of survival by studying one of Kabuto's jutsu, and in doing so she improves Lee's odds to 58%. Lee ultimately survives the procedure.

Being Hokage comes with a heavy workload, especially in the aftermath of Orochimaru's Konoha Crush, which left the village understaffed. For this reason, when Tsunade is informed that Sasuke has defected to Orochimaru, Shikamaru Nara - only recently promoted to chūnin - is the highest ranking ninja she can assign to lead the Sasuke Recovery Team; she allows him any genin he can recruit for the mission, though recommends Naruto's inclusion. After the Recovery Team leaves, Tsunade is notified of the Konoha Special Mission Platoon's defeat by the Sound Four, Sasuke's escorts. Having already suspected that a team of genin wouldn't be enough, she requests Sunagakure's support so that Orochimaru, a mutual enemy of both villages, can't gain Sasuke's Sharingan. She is also informed that Lee, despite still recovering from his surgery, has also gone off to lend support.

Despite the best efforts of the Recovery Team, Lee, and Suna's Three Sand Siblings, they are unable to stop Sasuke from joining forces with Orochimaru. Tsunade sends the Medic Corps to retrieve the Recovery Team's members and tend to their injuries; Tsunade, by studying the Nara Clan Medical Encyclopaedia, is able to cure Chōji Akimichi of the Three Coloured Pills' side-effects. Tsunade is later approached by Sakura Haruno, who asks to be taught medical ninjutsu. Sensing that Sakura has something she wants to protect (Naruto and Sasuke), Tsunade agrees.

Mizuki Tracking Mission
Jiraiya makes plans to take Naruto away from the village to train him. In the anime, Naruto must remain in Konoha while Jiraiya is off investigating and it is up to Tsunade to keep him preoccupied with other missions so that he won't go after Sasuke by himself. When, during one of these missions, the Legendary Stupid Brothers escape from prison, Tsunade convinces them to surrender with a quick display of genjutsu and her strength.

The Appearance of Strange Visitors
In the anime, Tsunade learns that Rock Lee and Might Guy are being impersonated by Mondai and Potcha. Deciding to have fun with the two, Tsunade pretends to believe their disguises and has them do many arduous tasks for her. The workload horrifies the two and eventually drives them away from the village.

In Naruto's Footsteps: The Friends' Paths
Sakura progresses rapidly under Tsunade's tutelage. In the anime, Ino Yamanaka also asks to train with Tsunade. From seeing the rivalry that exists between Sakura and Ino and how that competition drives them each to do better, Tsunade agrees. However, she teaches Ino only medical ninjutsu and not the additional skills she teaches Sakura, believing it would be better for Ino to focus on her clan's hiden jutsu.

About two years after Naruto leaves Konoha to train with Jiraiya, Tsunade proposes to Suna's Fifth Kazekage that their two villages hold a Chūnin Exam. Publicly, the exam will demonstrate the alliance that now exists between their two villages. Secretly, the exam will hopefully draw out Akatsuki, who are after jinchūriki like the Kazekage. The Kazekage agrees and the two villages split responsibilities for the exams. She sends Kakashi Hatake to invite Amegakure to the exams with instructions to investigate rumours that Ame's leader, Hanzō, has been overthrown. Ame accepts the invitation and Kakashi is unable to uncover anything, but both are convinced that something unusual is happening in Ame.

The first stage of the exams are completed in Konoha without incident. Before the examinees and proctors relocate to Suna for the second stage, Tsunade warns the Konoha personnel to be alert to attacks on the Kazekage. The Kazekage is indeed attacked during the second stage, forcing the exams to be cancelled prematurely. Performance reports on the remaining participants are sent to their respective villages to decide who will be promoted to chūnin; Tsunade promotes the members of Team 8, Team 10, and Team Guy. She also promotes Neji Hyūga to jōnin because of his role in protecting the Kazekage.

Kazekage Rescue Mission
Tsunade is informed of Naruto's return to Konoha after two-and-a-half years of training. She shares this news with Sakura and together they welcome him back. Tsunade has Naruto and Sakura reform Team 7 under Kakashi's leadership. While trying to find a mission to send Team 7 on that Naruto won't complain about, Tsunade receives a report that Suna's Fifth Kazekage has been kidnapped by Akatsuki. Tsunade decides to send Team 7 to lend assistance in the Kazekage's rescue in full awareness that Akatsuki wants to capture Naruto too. She isn't initially concerned, but when she suddenly wins the lottery she takes this as a bad sign and sends Team Guy to provide additional support.

A few days later they receive news that the Kazekage was successfully rescued and that Teams 7 and Guy will be returning to Konoha. Shizune questions the wisdom of sending Naruto into battle with Akatsuki, to which Tsunade replies that, because both Naruto and the Kazekage are jinchūriki, Naruto was the single best person for the mission.

Tenchi Bridge Reconnaissance Mission
When she gets back to Konoha, Sakura shares intel she's received of an opportunity to meet with a spy in Orochimaru's ranks, what may serve as an opportunity to find Sasuke Uchiha. Kakashi is left bedridden after the mission in Suna, requiring that new members be assigned to Team 7 to go meet the spy. Shizune once again questions Naruto's inclusion on the team, believing it would be safer to keep him in Konoha. Tsunade insists that Naruto is one of the few people she can trust with the mission with absolute certainty, and that besides it's a personal matter for him and he wouldn't allow himself to be excluded.

Tsunade is shortly afterwards summoned before the Konoha Council, with whom Shizune has shared her concerns and who also believe that Tsunade is deploying Naruto irresponsibly. Tsunade repeats her earlier reasoning, adding that Akatsuki will inevitably come for Naruto, and that if he keeps getting sent out on missions it will make it more difficult for Akatsuki to locate him. The Konoha Council relents after Tsunade promises to be held solely responsible in the event that her decisions and/or Naruto's capture endanger Konoha. They do, however, insist on including one of Danzō Shimura's underlings (Sai) on this new Team 7, which Tsunade agrees to. Tsunade also assigns an Anbu, codenamed "Yamato", to lead Team 7, partly so that he can keep an eye on Sai, but also because his wood release will help Naruto keep the Nine-Tails under control.

Although the new Team 7 does indeed meet Sasuke, they fail in bringing him back to Konoha. Naruto and the others are not deterred, however, and vow to to try again, which Tsunade approves.

Twelve Guardian Ninja
In the anime, Tsunade sends Team 7 to investigate some grave robberies near the Fire Temple. When they return, they report that the robbers, whoever they are, have a seeming interest in the graves of members of the Twelve Guardian Ninja. Because Sai was injured during the investigation, the Fire Temple allows Sora to fill in for him; Tsunade receives a confidential message that Sora's past and unusual powers pose a risk to the Fire Temple. Meanwhile, Tsunade has Danzō taken into custody on the suspicion that he is betraying Konoha to Amegakure. While she interrogates Danzō's apparent Ame-contact, the Konoha Council informs her that the man is a double-agent who has reported that the grave robbers may be after Sora.

The councillors recommend that Sora be either confined or eliminated. While Tsunade tries to decide what to do, Sora attacks her, but he is driven off by the arrival of Shizune and Naruto. The grave robbers soon afterwards arrive in Konoha, erecting a giant barrier around the village while earthen zombies attack. While most of Konoha's forces go on the defence, Tsunade sends Asuma Sarutobi to retrieve Sora. Sora eventually starts rampaging through the village with the Nine-Tails' chakra he has, and Tsunade prepares to confront him, but Naruto ends up dealing with it. Once the grave robbers are all defeated, Tsunade pardons Sora for his actions and allows him to leave Konoha.

Akatsuki Suppression Mission
Tsunade receives increasing reports of Akatsuki activity in other countries. She can't do anything until they enter the Land of Fire, but nevertheless starts making preparations. Once she receives news of Akatsuki's attack on the Fire Temple, Tsunade mobilises Twenty Platoons to find the Akatsuki members, capture them if possible, and, if capture is impossible, to eliminate them. Although one of the Twenty Platoons is able to find the Akatsuki members (Hidan and Kakuzu), both elude capture and Asuma Sarutobi is killed. A funeral is held in Konoha while the remaining Twenty Platoons continue the search.

Asuma's students on Team 10 leave Konoha to join the search and avenge him, which Tsunade tries to stop, citing among other reasons that they need a fourth member. Kakashi volunteers to accompany them, and Tsunade is forced to relent. Tsunade is aware that they'll need backup and starts looking for candidates; she has Sakura tell Naruto that, if he would like to go, he'll first need to complete the new jutsu he's been working on. He does indeed complete it and the Akatsuki members are ultimately defeated. Tsunade afterwards performs an autopsy on Kakuzu's body, examining the damage that Naruto's new Rasenshuriken did to it. From the cellular damage Kakuzu received, Tsunade concludes that the Rasenshuriken is as dangerous to Naruto as it is to his opponents and should therefore not be used again.

Three-Tails' Appearance
In the anime, Tsunade receives a dying Anbu's report about one of Orochimaru's bases. She puts Kakashi in charge of Team 8 and sends them to investigate. Because the mission has the chance of meeting Sasuke, Tsunade tries to keep Naruto from finding out about it. He finds out anyway, so Tsunade allows him and the rest of Team 7 to provide backup. Their teams later report encountering the Three-Tails, which Tsunade decides must be dealt with to prevent it from falling into enemy hands. She sends them instructions for a seal to place on the Three-Tails, some Konoha personnel to help perform the seal, as well as part of Katsuyu to provide additional assistance. Orochimaru's forces repeatedly interfere with the sealing, so Tsunade has some Anbu take over the sealing while the others return to Konoha. She later loses contact with the Anbu and the Three-Tails disappears, leading Tsunade to suspect Akatsuki's involvement.

Itachi Pursuit Mission
Jiraiya visits Tsunade and reports rumours that Orochimaru has been killed by Sasuke. They share these rumours with Naruto and Sakura, who suspect that Sasuke is making moves against his brother, Itachi Uchiha of Akatsuki. Naruto proposes that they try to locate Itachi so that they can, in turn, find Sasuke. Despite how unsuccessful previous attempts to capture Akatsuki members have been, Tsunade approves the formation of a combined Eight Man Squad to find Itachi.

Jiraiya visits Tsunade later with news that he's discovered the location of Akatsuki's leader, though he refuses to go into more detail until she meets him for drinks. While having saké, Jiraiya shares news of Amegakure's ongoing civil war, which the Akatsuki leader is rumoured to be behind. Because Amegakure is in a delicate political situation, Jiraiya must infiltrate the village by himself to confirm before Konoha can take direct action. Tsunade feels guilty for always relying on him to do dangerous work like this and reflects on happier times, before Orochimaru's apparent death and when he was still their friend. As Jiraiya prepares to leave, Tsunade instructs him to be sure to come back alive, fearing what his death might do to her.

Later, Shizune senses that Tsunade is worried about Jiraiya and tries to reassure her that he'll be fine. Tsunade replies he won't be back, which is a new tactic she's trying: she's betting on the one thing she doesn't want to have happen, relying on her bad luck to prevent her bet from coming true.

Six-Tails Unleashed
In the anime, Konoha receives reports of an attack on the Tsuchigumo clan and, as a consequence, their forbidden technique is at risk. Because the returning Eight Man Squad is closest to the Tsuchigumo clan's location, Tsunade sends Katsuyu to intercept them and give them their assignment to protect the Tsuchigumo.

Pain's Assault
Fukasaku, a former teacher of Jiraiya, reports to Tsunade that Jiraiya died while investigating the Akatsuki leader, Pain. Tsunade summons Naruto to her office so that Fukasaku can also tell him the news, who they expect will have greater difficulty. Naruto is indeed upset and blames Tsunade for his death, saying she should not have let him go. Sakura tries to stop him from storming out, but Tsunade lets him go. Tsunade makes investigating Pain's identity using the information Jiraiya gathered top priority: she has Shizune examine the Animal Path's body; she has Ibiki Morino interrogate the prisoner Jiraiya captured; she has Shikamaru Nara decipher the coded message Jiraiya left behind. When Shikamaru tries objecting to the assignment, Tsunade ignores him, leaves, and, once she's alone, she cries for Jiraiya.

Knowing that Pain will be coming for him, Naruto goes to Mount Myōboku to train with Fukasaku. The investigations into Pain's identity continue, but none are not completed prior to Pain's assault on Konoha. Tsunade sends orders for Naruto to be recalled to Konoha, but she's stopped by the Konoha Council, who feel that Naruto is safest where he is. Tsunade becomes angry with both councillors and berates them for lacking even the barest faith in Naruto's ability to save himself. The councillors are affronted by how she handles them and leave, but tell her to do what she wants. Tsunade heads to the roof of the Hokage Residence and summons Katsuyu, who she instructs to divide and attach to all of Konoha's villagers so that Tsunade can heal them remotely.

As Katsuyu's divisions spread throughout the village, Tsunade starts to fully appreciate the extent of the damage that Pain's attack is doing. When she senses, through Katsuyu, that Kakashi has died, she destroys a nearby spire out of frustration. Pain's Deva Path eventually finds her. As her Anbu-bodyguards move in to protect her, Tsunade recognises the Deva Path as an orphan that Jiraiya once trained. The Deva Path asks Tsunade where Naruto is, which she refuses to reveal. The Deva Path blames Konoha's past actions for the contemporary dire state of the world and Tsunade's refusal to cooperate with Akatsuki for the attack on the village. Tsunade is unmoved, but Pain is able to able to find out where Naruto is through other means. Before leaving, the Deva Path states it will show Konoha the pain that the rest of the world has known for too long.

The Deva Path leaps into the air and Tsunade tries to follow. As it destroys Konoha with Shinra Tensei, Tsunade transfers all of her chakra to Katsuyu to use in keeping the villagers safe. When the dust clears, Tsunade finds the village gone. She confronts the Six Paths of Pain and vows to personally defeat them. The Asura Path attacks her, which Naruto, newly returned, destroys in order to save her. Naruto asks Tsunade to trust Pain's defeat to him and has Gamakichi take Tsunade to Sakura. Having done all that she can and with her chakra gone, Tsunade's youthful transformation fades and she falls into a coma.

Fourth Shinobi World War: Countdown
After Tsunade regains consciousness many days later, she is immediately embraced by Shizune. As she eats to replenish her chakra reserves, Tsunade is told of all that's happened while she's been unconscious: Naruto's victory over Pain; Tobi of Akatsuki's declaration of a Fourth Shinobi World War; the formation of the Allied Shinobi Forces. Kakashi discusses these matters with her, and also thanks her for waking up in time so that he would not need to made her replacement as Hokage. Once she's done eating, she convenes a war council to discuss Konoha's strategies for the coming war and any preparations that will need to be made.

A few days later, Tsunade travels to Kumogakure to meet with the other heads of the Alliance and discuss topics of broader importance. Chief among these is what to do with Naruto and Killer B, whose capture Tobi started the war for. The Alliance's other leaders have already decided to send them into seclusion, which Tsunade strongly disagrees with, believing they would be invaluable on the battlefield. The Fifth Kazekage quickly disagrees, reminding her that Naruto has the tendency to be reckless for his friends, which in turn would place him too much at risk. Knowing she was overruled, Tsunade reluctantly agrees and Naruto and B are sent to the Island Turtle. In the anime, after the meeting with the other heads of the Alliance she requested that B teach Naruto to achieve control over the Nine-Tails in the event that they would have to be deployed, which A approved. As they move on to other matters, Tsunade takes particular interest in equipping the Logistical Support and Medical Division with enough supplies.

Power
In the anime, Tsunade sends Team 7 to investigate the massacre of the Tonika Village. When Team 7 reports Kabuto Yakushi's use of the Impure World Reincarnation, Tsunade sends them all available backup.

Paradise Life on as Boat
In the anime, Tsunade sends Sakura to Benisu Island to collect medicinal herbs for the war effort. She later refuses Konohamaru Sarutobi's request to join the Allied Shinobi Forces.

Fourth Shinobi World War: Confrontation
Most of the Alliance's leaders head to the battlefield when the war begins, but Tsunade and the Fourth Raikage remain at the Allied headquarters to discuss tactics, coordinate troop movements, and process new intel. On the first night of fighting, they receive reports that Naruto and B have escaped the Island Turtle. The Raikage takes Tsunade with him to head them off; she leaves behind one of Katsuyu's divisions in case she needs to be contacted about anything.

Once they locate Naruto and B, the Raikage blocks their progress and tries to convince them to return to the Island Turtle. Naruto implores Tsunade to let them pass, but she explains that she must do what is in the best interest of the entire Allied Shinobi Forces. Naruto's continuing obstinance prompts the Raikage to decide to kill him so that Akatsuki can't capture him. Tsunade cannot allow this and steps in, observing that Naruto's new Nine-Tails Chakra Mode indicates his unprecedented control over the Nine-Tails, something that may never be replicated in future jinchūriki of the Nine-Tails. The best course, she argues, is to let Naruto use his new power to try and win the war. The Raikage is not openly convinced by Tsunade's, B's, or Naruto's words and appears willing to fight, but when Naruto is finally able to get past him the Raikage doesn't pursue.

When Tsunade and the Raikage return to headquarters they are informed that the White Zetsu Army is cultivated from the DNA of Hashirama Senju. Tsunade is upset by the continued use of her grandfather's abilities and what else Tobi may have used them for, but believes Naruto may be able to root out Zetsus that have infiltrated the Allied Forces.

Fourth Shinobi World War: Climax
Naruto, using shadow clones, does indeed help defeat the Zetsu Army, finding those that are disguised, defeating those that aren't, and helping capture any remaining reincarnated forces. The apparent victory is cut short by the sudden appearance of the reincarnated Madara Uchiha, who proceeds to decimate the Fourth Division. Wishing to join the battle, Tsunade has Mabui transfer her to the site of Madara's battle with the Fourth Division, using Creation Rebirth to heal the damage that the transfer does to her body. The Raikage joins her and they arrive in time to save the Fifth Kazekage and Third Tsuchikage from Madara's attack. Tsunade heals them and, after being joined by the Fifth Mizukage, the Five Kage face off with Madara. Confident they can defeat him, they tell one of Naruto's shadow clones to entrust Madara to them and to go defeat Tobi elsewhere. Tsunade initially takes a supplementary role during the battle, healing the other Kage's injuries and replenishing their chakra as needed. She is surprised when Madara is able to use her grandfather's wood release, which they eventually discover to be due to a cloned graft of Hashirama's face that has been implanted in Madara's body. Madara senses that Tsunade is descended from Hashirama and decides to kill her first because she is so much weaker than her ancestor. She acknowledges that she did not inherit all of Hashirama's natural gifts, but she does have his Will of Fire, which drove her to create the Ninja Art Creation Rebirth — Strength of a Hundred Technique. After activating the technique, she joins the other Kage in attacking him. Madara is unimpressed, but Tsunade is nevertheless able to punch through his body, giving the Kazekage a chance to try and seal him.

Madara eludes capture and uses Susanoo's sword to stab Tsunade. Madara assumes she's dead, but Tsunade removes the sword from her body and attacks him with it, convincing him that maybe she did indeed inherit something from Hashirama. He in fact admits that all the Kage have posed him some challenge, but claims that it's because they outnumber him five-to-one; in order to make things "fair", he creates twenty-five wood clones, five for each of the Kage to fight. The wood clones each use Susanoo and fight the Kage into the night. Despite the superior forces against them, the Kage are able to combine forces against the original Madara, impressing him enough to use Susanoo's "Complete Body" form. Before he can use it to destroy the Kage, the Impure World Reincarnation is released and Madara's soul starts returning to the Pure Land.

Madara uses the remaining moments before his soul departs trying to finish off the Kage. Tsunade takes responsibility for blocking his attacks, expecting that her Creation Rebirth will heal the damage, but she runs out of chakra and is left at Madara's mercy. She is saved by Dan Katō's Spirit Transformation Technique, his soul having also been released from the Impure World Reincarnation. Tsunade uses the little time that they have apologising to him for abandoning his dreams for so many years after he died, but that she now tries to keep his dreams alive in her capacity as Hokage. He thanks her for continuing his dream, but tells her that the greatest service she can do to him is to stay alive, as she herself is his dream. He kisses her forehead before vanishing and transfers all of his chakra to her. Although Tsunade is rejuvenated, Madara has used this time removing the Impure World Reincarnation's user's control over him, thus allowing him to stay.

Now free to do what he wants, Madara decides he's lost interest in the Kage and states his intentions to go after Naruto. The Kage try to stop him and thus fulfil their promise to Naruto, but Madara defeats them all and leaves them near death. Tsunade, despite being bisected in the battle, is able to summon Katsuyu. She asks Katsuyu to bring the other Kage closer to her so that she can try and save their lives. Tsunade is later found by Orochimaru, Suigetsu Hōzuki, and Karin. Tsunade has used almost all of her chakra on the other Kage and now lacks the energy to even speak. After assuring Katsuyu that he wants to help, Orochimaru has Karin replenish Tsunade's chakra and has Suigetsu assist Katsuyu with putting Tsunade's halves back together. Tsunade reluctantly thanks Orochimaru once she's restored and notes a change in him, a change that might have saved Jiraiya had it happened sooner. Orochimaru departs, leaving Tsunade to finish healing the Kage.

Birth of the Ten-Tails' Jinchūriki
Once all the Kage are healed, the Kazekage transports them to where the Allied Forces are fighting; along the way, Katsuyu informs them of what's been happening up until now. As they near the battlefield, a reincarnated Hashirama Senju contacts all the Allied powers. After briefly saying hello to Tsunade, Hashirama reveals the purpose of the God Tree recreation now looming over them: to cast the Infinite Tsukuyomi. Much of the infantry is thrown into disarray from fear of what will happen, but when the Kage finally arrive they rally their forces against the God Tree. Tsunade locates Sakura and teams up with her to summon a large segment of Katsuyu, which dissolves across the battlefield so that Tsunade and Sakura can constantly rejuvenate everybody as they fight.

Although they aren't able to cut down the God Tree, the Allies are able to help Naruto defeat Tobi, real name Obito Uchiha. Naruto leaves to fight Madara, leaving the rest of the Allied Forces to fight another Zetsu. Tsunade lacks the chakra necessary to participate in the fight, much less continue performing medical ninjutsu. For this reason, when the Kazekage brings Naruto to her in need of emergency life support, Tsunade sends Sakura to help him.

Kaguya Ōtsutsuki Strikes
Despite the Allied Forces' efforts, they are unable to stop Madara from casting the Infinite Tsukuyomi, trapping the world in a dream. Tsunade dreams of a Konoha where Dan is Hokage, where Nawaki and Jiraiya are still alive, and where Orochimaru never defected from the village. In the anime, while waiting to join Dan for a Kage Summit, she reads a novel written by Jiraiya titled Jiraiya Shinobi Handbook: The Tale of Naruto the Hero, despite her telling him she had no interest in it earlier. In the novel, Konoha went through much less upheaval; the Fourth Hokage and his wife survived the Nine-Tails' Attack on Konoha, and the Uchiha Clan Downfall never happened. Naruto and Sasuke eventually release the Infinite Tsukuyomi, freeing Tsunade and the rest of the world and thus ending the Fourth Shinobi World War.

Kakashi Hiden: Lightning in the Icy Sky
Kakashi is appointed the Sixth Hokage after the Fourth Shinobi World War ends. Yet a year after the war is over, he still has yet to officially accept the duties of the office. Tsunade continues to carry out all the responsibilities until he's ready, but also pressures Kakashi to make a decision. Kakashi requests that she wait until he completes his mission to guard the Tobishachimaru on its top secret maiden voyage. The Tobishachimaru ends up being hijacked by the Ryūha Armament Alliance during its voyage, and the hijackers threaten to kill the passengers if Konoha doesn't release their leader, Garyō, from the Blood Prison in Kusagakure; they also stipulate that Naruto not be involved. After being informed that Kakashi is aboard the Tobishachimaru, Tsunade summons Konoha's available personnel, with the exception of Naruto.

While trying to plan what to do, Tsunade is contacted by the Third Tsuchikage, who informs her that the "secret" Tobishachimaru is visible from several countries, including his own Iwagakure. Although she assures him it is bound for Kusa, he warns her that he will need to destroy it if it threatens his village, which would complicate the relationship between Konoha and Iwa. Tsunade shares this threat with one of the hijackers, Rahyō, but it does not deter him. Having few options left, Tsunade decides that the ship must be destroyed before Iwa is forced to intervene. She has Ino Yamanaka tell Kakashi to do what he can but also warn him of her decision. She leads the assembled available Konoha ninja to the Blood Prison to be on hand in case the worst should happen.

Kakashi ultimately crashes the Tobishachimaru just outside the Blood Prison, thus averting an incident with Iwa. However, several passengers died during the hijacking and the entire incident has been an embarrassment to Konoha. Tsunade is outraged by these developments and orders Kahyō, the highest-ranking hijacker to survive, taken into custody. Kakashi intervenes, asking that he be allowed to pass sentence on Kahyō instead. Tsunade allows it on the condition that Kakashi make it his first act as Sixth Hokage, which he agrees to.

After the war, Tsunade studies the material that the White Zetsu are made of, and from her research is able to create prosthetic arms for Naruto and Sasuke, though Sasuke declines his.

The Last: Naruto the Movie
Two years after the Fourth Shinobi World War, Tsunade oversees the evacuation of the Land of Fire's citizens to a fallout shelter to escape the crashing Moon. Naruto ultimately prevents the disaster, the announcement of which Tsunade happily listens to.

Sakura Hiden: Thoughts of Love, Riding Upon a Spring Breeze
Tsunade meets Sakura for drinks, partly to congratulate her for her recent work with the Konoha Hospital, but also to try to convince Sakura to take it easy, as she's been working harder than she needs to. Sakura changes the subject to asking how to gain men's attention. When Tsunade can't offer her any specific advice, Sakura asks that Tsunade bet against her love life, hoping for Tsunade's bad luck to play in her favour.

Sakura later meets with Tsunade for drinks again, where she shares rumours that someone with Sasuke Uchiha's appearance and chakra signature is conspiring against Konoha. The appearance is easily faked, but the chakra signature has Sakura stumped; she asks Tsunade if it would be possible to reproduce someone's chakra signature by gathering large amounts of skin and hair that naturally fall off. Tsunade deems the idea plausible. Sakura is reassured and Tsunade tells her she's happy to help, but she reminds Sakura that she's retired and that she should try to figure things out for herself.

Konoha Hiden: The Perfect Day for a Wedding
Tsunade attends Naruto's marriage to Hinata Hyūga. Yamato runs around prior to the ceremony making final preparations, which Tsunade occasionally offers advice on.

New Era
In later years, Tsunade continued to stay close to Naruto, watching his growth as both a family man and the Seventh Hokage. She also came to know Naruto's children, especially terrifying Boruto with her temper while scolding him. Twelve years after Naruto's wedding, while a Five Kage Summit was being held in Konoha, Tsunade and the other retired Kage visit the Third Tsuchikage to, as Tsunade puts it, get drunk and complain about things.

Mitsuki's Disappearance Arc
In the anime, when two chūnin gate guards were attacked by unknown assailants, the village was put on lockdown. Tsunade soon after returned from her trip to meet with Naruto about the events. She then joined him when Ino probed a guard's mind for answers, learning that Mitsuki had left willingly with the attackers. When Tsunade asked who this boy is, Naruto revealed that Mitsuki was in fact Orochimaru's son. Tsunade was furious that Naruto would permit an offspring of the man who killed the Third Hokage live in Konohagakure, let alone keep it a secret from her. Naruto rationalised this on the grounds that Orochimaru's conduct as changed from before and that his aid in investigating the Ōtsutsuki is invaluable. Despite this, noting the unpredictable nature of Orochimaru, the meeting ended with deeming the Oto-born boy as a threat. As the council and Hokage continued to talk about how best to deal with this, Tsunade concluded that it was a waste of time to discuss the merits of Naruto's decision to allow Mitsuki into the village, and they should focus instead on how to deal with the current situation.

As Tsunade continued to keep word about Mitsuki quite and the council from taking drastic actions, questions continued to build up on Mitsuki as Naruto and Shikamaru still felt the situation didn't make sense for Mitsuki to betray them. They began wondering if the enemy's goal was Mitsuki himself because of his unique background. They then received word that one of the guards was recovering and would soon awake to give them answers.

When Shikadai contacted his father via phone, he revealed that Iwagakure was taken over as part of a plan by Ōnoki. Knowing that they couldn't act hastily, Kakashi and Tsunade were sent to meet with the other Great Villages to get their support on engaging this personal matter.

Time Slip Arc
In the anime, when a grown-up Sasuke and Naruto's future son Boruto were sent back in time to shortly after Sasuke's defection, the two bumped into Jiraiya and Naruto. After Jiraiya framed the two for his discovered peeping, but Tsunade arrived and resolved the situation.

Tsunade asked about Boruto and Sasuke's arrival, and Sasuke claimed they were travelling performers who utilised ninjutsu during their performances. Still somewhat suspicious, Tsunade ordered Naruto and Jiraiya to guard Boruto and Sasuke, proclaiming that a recently defected genin, as well as Konoha still recovering from an assault during the Chūnin Exams, they needed to remain on their guard at all times, and couldn't afford to let strangers walk into their village. Later, Tsunade assigned all the Konoha genin to clean up the bathhouse to make up for the commotion Naruto and Jiraiya caused there.

Days later, after Sasuke and Boruto completed their mission to defeat Urashiki Ōtsutsuki, Sasuke used his Sharingan to erase Tsunade's memories of the events to protect the timeline.

Naruto Shippūden the Movie
The demon Mōryō raises an army of stone warriors in an attempt to take over the world. Tsunade sends most of Konoha's forces to fight these warriors. She also sends a team consisting of Naruto, Sakura, Neji Hyūga, and Rock Lee to guard Shion, a priestess who can stop Mōryō.

Naruto Shippūden the Movie: The Will of Fire
Hiruko, a former friend of the Sannin, declares the start of the Fourth Shinobi World War. Due to how he makes his announcement, the other villages come to believe that Konoha is aiding Hiruko's schemes and so start amassing against Konoha. While Tsunade tries to defuse the situation, Kakashi confides in her that he met Hiruko many years ago and was branded with a mind-controlling technique that will force him to go to Hiruko. Knowing that this will happen soon and that Hiruko will at some point try to take his Sharingan, Kakashi asks Tsunade to place a seal on him that will activate his Mangekyō Sharingan when Hiruko tries to do so, thus killing him and preventing war. Tsunade complies and, once Kakashi is gone, she declares him a missing-nin to keep his plans a secret. She forbids anyone from going after him, but Naruto ends up ignoring her.

Naruto the Movie: Blood Prison
When Naruto is accused of trying to assassinate the Fourth Raikage, Tsunade orders he be imprisoned in the Blood Prison despite his claims of innocence. Tsunade is fully aware that Naruto did nothing wrong, but needs to follow through in order to draw out a conspiracy rooted in the Blood Prison. Once the conspiracy is exposed, Tsunade leads Konoha's forces in rescuing Naruto from his wrongful imprisonment.

Road to Ninja: Naruto the Movie
The Tsunade of the Genjutsu World wears glasses, is flat-chested, and is fairly responsible. Whereas the real Tsunade looks younger than her age, this Tsunade looks older than her age.

Trivia

 * Tsunade and the other Sannin are named after the characters in the Japanese folktale Jiraiya Goketsu Monogatari. Tsunade of that story excels in slug magic.
 * means "mooring rope", which is not dissimilar to her brother's name, Nawaki, which means "rope tree".
 * Tsunade is first mentioned by Tenten in chapter 84 of the Naruto manga, which was 55 chapters before her first formal appearance.
 * Studio Pierrot's Settei sheets of Tsunade show that she was 145 cm when she was part of Hiruzen's genin team, and that her high-heeled sandals she wears as an adult add 5 cm to her height.
 * According to the databook(s):
 * Tsunade's hobby is gambling.
 * Tsunade wishes to fight Naruto Uzumaki.
 * Tsunade's favourite foods are chicken breast and sake, while her least favourite food is liver sashimi.
 * Tsunade has completed 1,256 official missions in total: 40 D-rank, 236 C-rank, 467 B-rank, 418 A-rank, 95 S-rank.
 * Tsunade's favourite phrase is, referring to getting rich without much effort.
 * Tsunade shares her blood type with her former team-mates, Jiraiya and Orochimaru.
 * While Tsunade's English anime voice actor is Debi Mae West, in some games, she is voiced by Mary Elizabeth McGlynn, who is Kurenai Yūhi's voice actor.
 * In Clash of Ninja Revolution 2, McGlynn voiced Tsunade throughout the story-line while West voiced Tsunade during the actual gameplay.
 * Tsunade is the only Hokage to live long enough to see two generations of successors take office.

Quotes

 * (To Jiraiya about Naruto) "Jiraiya, are you the one who taught him the Rasengan? Are you acting like a teacher by teaching him something he can't master? Don't give him any ideas! That's why this kid likes to daydream that he's going to become Hokage someday."
 * (To an unconscious Naruto) "It's because to be Hokage… is your dream… isn't it, Naruto? One last time… just one last time… I place the odds on you."
 * (To Shikamaru) "Grow up… Death comes with being a shinobi… There are times when death is hard to accept, but if you don't get over it, there's no future…"
 * (To the Konoha Council) "People like Jiraiya… and Sarutobi, and Elder Chiyo of Suna possessed something you two sorely lack. Do you know what that is!? …Faith! My grandfather, the First Hokage, believed in you and entrusted you with the village. Now it's your turn to believe in these children and entrust it to them!"
 * (To Pain) "I am the Fifth Hokage… You've trampled on our ancestors' treasure… their dream… And you will pay the price! As the Hokage, I will put a stop to you here and now!"
 * (To Madara) "Although I am a descendant of the First Hokage, it's true that I don't know how to use Wood Release. And compared to him, who was able to use medical ninjutsu without even making seals, it's true that my own ninjutsu is nothing to brag about. And it's true that I'm a woman… but I'm definitely not a weak woman… What I inherited from my grandfather isn't just simple 'power'. My true strength comes from that which was passed down from the First to each generation afterwards… Don't underestimate the Will of Fire!"