Tsunade

is the of Konohagakure. She succeeded the position after the death of her teacher, Hiruzen Sarutobi. She, along with Orochimaru and Jiraiya, are recognised as "The Legendary Sannin of Konoha".

Background
Tsunade is the granddaughter of the First Hokage, Hashirama Senju, and grandniece of the Second Hokage, Tobirama Senju, leading others to call her. She, along with Jiraiya and Orochimaru are former students of the Third Hokage. Like Team Kakashi, Tsunade and her teammates were given the bell test. When Jiraiya lost and was tied to a log, she taunted him before leaving.

At some point, when she caught Jiraiya peeping on her while she was in the hot springs, she proceeded to break both of his arms, six of his ribs and ruptured several internal organs as a punishment for being a pervert. Ever since then, Jiraiya has been very careful to suppress his perverted ways around Tsunade. Jiraiya mentions that this is one of the two times he has ever been close to death.

During the Second Shinobi World War, Tsunade and her former team-mates fought Hanzō, who gave them the title of Konoha's as a reward for surviving their battle. On their way back to Konoha, they encountered the Ame Orphans, who Jiraiya chose to train. Throughout the war, she would become famous for frequently counteracting Chiyo's poisoning attempts, earning contempt from Chiyo because of it. Furthermore, according to Jiraiya, Tsunade was the reason Konoha won the war.

On her brother's twelfth birthday, Tsunade gave him their grandfather's crystal necklace in the hopes that it would help him achieve his dream of becoming Hokage. The next day, he died as a casualty of the war, which returned the necklace to Tsunade's possession. This event resolved Tsunade to advocate for the inclusion of medical-nin to be incorporated into teams that were on the battlefield. Some time afterwards, Tsunade fell in love with a man named Dan Katō who also wanted to become Hokage. As a sign of her affection, and in the hopes that this time it would help make his dreams come true, Tsunade gave him the necklace as well. Dan died a bloody death during the course of the war, once again returning the necklace to her possession. Dan's death caused her to develop hæmophobia, which made her unfit to take part in any more battles. Dan's death also led people to believe that the necklace was cursed; causing death to anyone who wears it except Tsunade.

With the deaths of the two she loved the most, Tsunade came to lose faith in the title of Hokage, believing that only fools would want such a position. With these changes of ideals, Tsunade left Konoha with Dan's niece, Shizune, taking her on as her apprentice who became one of the few people Tsunade trusts with absolute certainty. Tsunade also came to own a pet pig, Tonton which she leaves mostly to Shizune's care.

Personality
When she was first introduced, Tsunade was cynical of anyone with dreams, especially those who want to become Hokage. After meeting Naruto, she realises that this cynicism is insulting to the memories of both Dan and Nawaki. After seeing Naruto's conviction to become Hokage and proving her wrong in his ability to learn the Rasengan, she has a change of heart. Despite her still blunt attitude towards Naruto, she has come to care for him deeply and puts her faith in him for the future, even agreeing to take on the mantle of Hokage herself, carrying on the dreams of Dan and Nawaki. As Hokage, Tsunade has shown the same level of loyalty to the village that previous Hokage held; during the invasion of Pain, she released all of her chakra in order to save the lives of thousands of people within Konoha, at great personal risk. Tsunade also has a great deal of faith in the next generation, and sees the potential that Naruto and the rest of the Konoha 11 hold.

Tsunade typically projects a tough demeanour, even when facing great personal difficulty. She readily criticizes others for their faults, such as Naruto's immaturity or Jiraiya's perversion, though her habits are rarely any better. Beneath this tough exterior, Tsunade truly loves her village and its people and will at times show sympathy for others, consoling Shikamaru that, while he failed his mission to return Sasuke to Konoha, all of his team-mates survived. This is also shown when she worked hard in order to help heal Rock Lee, so that he might continue to be a shinobi. In life-threatening or important situations that involve putting someone she cares for in danger, she tends to get angry with people who disagree with her plan, such as the restrictions the Konoha Elders placed on Naruto, or the argument on whether Naruto and Killer B should participate in the Fourth Shinobi World War, even calling Gaara a "little punk" when he disagreed with her.

Tsunade also has a firm belief that Naruto, and all jinchūriki, are not tools of war and are their own people. She has always voiced that Naruto is a great shinobi and should be used by the village as any other shinobi would be. This value is so strong in Tsunade that she yelled at the other Kage for not allowing Naruto and Killer B to fight in the Fourth Great Shinobi War. Although she eventually agrees to keep the jinchūriki away from the battles, she is outraged when A decides to kill Naruto to prevent him entering the war. Tsunade then turns on A, saying that they need to use the jinchūriki in the war if they are going to win. This shows her great faith in Naruto's abilities to end the war, and her great courage as she is willing to challenge powerful shinobi like the Raikage in order to let Naruto and Bee pass.

Tsunade is also a compulsive gambler, who has the unfortunate disadvantage of having terrible luck. As a result, she has been elevated to a comical status as because of the gross profits others have made off of her misfortune and gambling addiction. In the rare instances that Tsunade hits a winning streak, she believes it to be a bad omen, and bad things do tend to happen to her or her comrades afterwards. The symbol on the back of her coat,, means "gamble", or "wager", as gambling is one of her favourite pastimes.

Despite Tsunade shunning all of Jiraiya's romantic advances over the years, she showed signs during their last conversation that she may have had deeper feelings for him as she would blush at several comments he made to her, but was constantly angered by Jiraiya's perverted nature. Regardless, Tsunade still cared very much for him as one of her oldest friends. While he is in Amegakure investigating Pain, she bets that he will die so that her terrible luck will ensure he survives. When she finds out he has died, she thinks back on their time together and cries for the loss of her dear friend.

Appearance
Tsunade is a fairly tall light-skinned woman with light brown eyes and straight blonde hair. Her hair is waist-length with shoulder-length bangs framing both sides of her face. As a child, she had it tied in a high ponytail. As an adult, it is usually tied into two loose ponytails. Sometime after leaving the village, she obtained a violet rhombus on her forehead similar to her grandmother's, which she uses as a chakra gathering point known as the Yin Seal. It will temporarily disappear when unleashing the conserved chakra.

While only in her early fifties, her form is a frail and wrinkled old appearance, more so than her age would suggest. However, she maintains the appearance of her younger self through a unique and constant Transformation Technique. In her youth, the appearance she normally takes, she had a slender yet noticeably curvaceous frame. Despite being known as flat-chested in her childhood, she now has a rather sizeable bust; 106 centimetres, according to Jiraiya. Her beauty has been pointed out several times and she's been called the most beautiful kunoichi in the world by several people.

She often wears a grass-green robe with the kanji for written in black 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 sandals with high heels and polish on both her fingernails and toenails. She also wears a soft pink lipstick. She also used to wear the First Hokage's Necklace in clear view on her chest, before giving it to Naruto Uzumaki.

Abilities
As one of the Sannin and the Fifth Hokage, Tsunade is one of the most powerful shinobi that Konoha has ever produced and a remarkable combat medical-nin. She is also hailed as the world's strongest kunoichi. Jiraiya commented that no one could stand equal to her in terms of combat and medical prowess. In the anime, she has shown some skill at genjutsu, able to bind multiple targets at once.

Taijutsu
Tsunade's trademark ability is her incredible raw strength that greatly defies her highly feminine built, and superb taijutsu skill, the former of which is great enough to launch her targets several meters with a mere finger flick or create fissures with a single finger jab at the ground. An opponent struck by her could suffer damage ranging from broken bones, ruptured organs, or even death, as Jiraiya learned for his perverted actions in his youth. While a medical-nin normally tries to avoid direct battle, Tsunade’s close-range combat skills have been considered unsurpassed, able to skilfully wield a kunai with a single finger; this was made so mainly to intimidate her opponents from approaching her.

As a field medical-nin, Tsunade is highly skilled master of evasion. This is to keep herself alive in battle so she may aid her team-mates; a skill she drilled into Sakura while training her as well. While not her most prominent trait, she is quite fast and equally fierce in battle, having displayed high levels of quickness to the point that her opponents find her an overwhelming adversary. She was able to incapacitate Shizune with a quick strike before she could react, use the Important Body Points Disturbance technique on Kabuto when he thought she was incapacitated, block Orochimaru from attacking an unconscious Naruto even though severely wounded, and even intercept Manda mid-bite while lifting Gamabunta's sword.

Additionally, Tsunade has showcased incredible durability feats, both physically and mentally. She was still able to move after having her muscles torn, something Kabuto himself found impressive and praise-worthy. Furthermore, after being stabbed straight through the chest, her left shoulder, and her abdomen, she survived the normally fatal damage and still managed to land an attack on Orochimaru. Likewise, her mental stability is so great that she was able to overcome her paralysing fear of blood through willpower alone, something every eyewitness found miraculous.

Intelligence
While normally appearing carefree or short-tempered, as the leader of her village, Tsunade is a capable leader. A keen thinker, Tsunade has repeatedly been seen highly observant and analytical, allowing her to see through most deceptions and is rarely caught off-guard. Most commonly, Tsunade will choose the best shinobis available to construct a team after looking over the assigned mission. Also a very experienced shinobi, Tsunade has advanced understanding in the flow of chakra and various techniques. In the anime, she was able to analyse and replicate the basic mechanics of Kabuto’s regeneration technique to aid Rock Lee in his life-risking surgery. In battle, she has shown great resourcefulness and ingenuity, able to quickly pick up on her opponent's fighting style and battle rhythm to better avoid damage.

Her intelligence is most renowned as the best in the world for her expertise in all areas of medicine. Her knowledge of the medical arts are so vast that she can immediately determine what kind of injuries or illness (physical or mental) a person has from a single glance. In addition to this, Tsunade seems to have a vast knowledge of poisons and herbal medicine, as noted by Chiyo. She also has remarkable knowledge of the human psyche, as she was able to effortlessly undo the damage to Kakashi and Sasuke's minds. During the Second Great Shinobi War, Tsunade was the only one capable of countering all Chiyo's poisons. Tsunade has also proven to be a very capable teacher, having single-handedly trained Sakura and Shizune and passed on much of her knowledge make them become two of Konoha's best medical-nin and field support.

Chakra Reserves and Control
Tsunade has shown to have rather large supplies of chakra. Despite advanced medical techniques being very taxing on chakra, Tsunade has shown able to heal countless people at a time and use her chakra to maintain her Creation Rebirth technique for an extended battle. During Pain's invasion, Tsunade was able to easily transfer portions of her chakra throughout the village to heal and save most of the inhabitants. Even more impressive than her reserves is Tsunade’s control. Since a young age, Tsunade excelled in all forms of chakra manipulation; even able to maintain multiple techniques at once. Her innate talent for it allows her to gather her chakra from any part of her body with such precision and perform any technique to their maximum potential without any wasted chakra or timing.

Her signature ability with chakra control is to instinctively amplify her already legendary strength with chakra control to monstrous levels, allowing her to perform feats like causing gigantic craters with a simple punch or kick to the ground, and launch Gamabunta's tantō into the air and then guide it down right into Manda's mouth. This is done by building up and releasing her chakra with precise timing upon impact, making it effortless for her to decimate any target.

Transformation Technique
Even though she is in her early fifties, Tsunade's Transformation Technique makes her appear as if she were still in her twenties (which Naruto calls "living a lie"). She readily alters what age she appears in order to avoid her gambling debts. Tsunade's transformation is somewhat different from a normal transformation, as it seems to be permanent, not getting dispelled when she is slashed or injured, and she apparently does not need to exert any effort to stay transformed. The transformation dispels when she runs out of chakra, reverting her to her natural appearance.

Medical Ninjutsu
Much of Tsunade's fame comes from her being able to perform any procedure flawlessly to cure and heal injuries that others would consider impossible or a lost cause with little effort. She can do so through the usage of no more than chakra or basic tools. She healed the psychological damage caused by Tsukuyomi, the damage done to Rock Lee's spine, and counteracted the effects of the Three Coloured Pills. Tsunade has also been noted to be capable of making a powerful sleeping potion, an ability that she passed on to her student, Sakura Haruno. Jiraya also states that Tsunade is the only shinobi who could spike a drink without a shinobi knowing it.

With her remarkable knowledge of the human body and converting her chakra into electricity, Tsunade is capable of sending electric waves into the opponent's nervous system by striking the back of the neck. This then scrambles the electric signals within them and disrupts the way their body moves, such as attempting to move the right hand would cause the left leg to move instead, and so on. It is unknown if this is Lightning Release. In a similar manner, she can use a single chakra-infused strike to effortlessly cause internal damage or incapacitate a target as she did the latter to Shizune when she tried to stop Tsunade from meeting with Orochimaru.

The most extreme example of her medical prowess is her Creation Rebirth, a technique that makes use of the massive amounts of chakra available after using Yin Seal: Release to continuously regenerate the cells in her body, healing any wound and even growing back missing organs. It gives her a form of "immortality" in battle that even Orochimaru expressed envy for. However, because of the rapid cell regeneration, the technique shortens her life. Because of the risk associated with the technique, Tsunade only uses Creation Rebirth in extremely desperate situations. This technique is considered as the absolute pinnacle of medical ninjutsu, and Tsunade developed it under the resolution of protecting those dear to her.

Fūinjutsu
Tsunade is also well-versed in fūinjutsu, capable of using an S-rank seal to continuously store up chakra reserves for various high-level techniques such as being the basis to extend her Creation Rebirth technique's time limit. Her highly knowledge in removing seals. Furthermore, Orochimaru believed she could undo the effects of the Dead Demon Consuming Seal, which Tsunade and Shizune made no attempts to refute. In the anime, she designed a technique to seal a tailed beast from scratch. In the anime, Tsunade also demonstrated considerable skill in Space–Time Ninjutsu, as she was able to teleport one of Katsuyu's divisions to Team Kurenai's location despite the great distances.

Slug Affinity
Tsunade can summon slugs of varying sizes, although she has only ever been seen summoning Katsuyu. The slugs' primary abilities seem to revolve around spitting acid and splitting into smaller slugs. Tsunade apparently has a mental connection with Katsuyu, as she was able to get reports and send out messages through Katsuyu during the invasion of Pain. Tsunade can transfer her chakra to a large number of slugs over long distances. By having the slugs spread out and attach themselves to wounded individuals, Tsunade is then capable of healing multiple injuries at different locations simultaneously.

Search for Tsunade Arc
After his failed invasion of Konoha, Orochimaru sought out Tsunade. Upon finding her, he asked her for a favour, though before he could specify what this favour was, she declined, having already noticed his wounded arms. Trying again, Orochimaru asked her to heal his arms. Kabuto then complemented Tsunade saying that she's the only one in the world who can cure Orochimaru or kill him. Tsunade noticed that Orochimaru's injury is caused by a powerful seal and when she asked him he replied explaining that the injury was a result of his carelessness when killing the Third Hokage. Shocked by this revelation, Tsunade prepared to kill Orochimaru, though he once again intervened by offering to resurrect her dead loved ones: Dan "her lover" and Nawaki "her little brother" in exchange. Interested in this offer, Tsunade considered it and was left a week to decide.

Soon afterwards, Tsunade was approached by Jiraiya, who wanted her to become the next Hokage. After turning down the offer and ridiculing it, Naruto challenged Tsunade to a fight, enraged that someone could disrespect the title of Hokage in such a manner. Tsunade accepted, and easily won, though not before witnessing Naruto's attempt at using the Rasengan. Intrigued, Tsunade made a bet with Naruto to master the technique in a week; if he won, he would get the First Hokage's necklace, and if Naruto did not master the Rasengan within a week, Tsunade would get all the money he was carrying. Naruto accepted the bet, and resumed his training. As the week progressed, Tsunade kept a careful eye on Naruto's progress, and all the while contemplated Orochimaru's offer. When the week was up, and Naruto appeared to have failed in mastering the technique, Tsunade went to meet Orochimaru, first drugging Jiraiya to make sure he didn't interfere.

Upon meeting with Orochimaru, Tsunade asked that he not destroy Konoha when his arms were healed. Orochimaru agreed, and Tsunade prepared to heal him, though was interrupted by Orochimaru's assistant, Kabuto Yakushi. Kabuto, being a medical-nin himself, was able to notice the killing intent of Tsunade's healing technique, and as such, knew that she really intended to kill Orochimaru. Her motives known, Tsunade revealed that she knew Orochimaru had lied when saying he'd leave Konoha alone, and that she couldn't bring herself to allow it, due to Nawaki and Dan having loved Konoha until the end of their days. While she had tried to forget this fact over the years, Naruto's determination and desire to be Hokage reminded her of their dreams, and she had decided to do whatever was necessary to protect those dreams.

With that, Tsunade attacked Orochimaru, though Kabuto fought her in his place. As the two traded blows, Kabuto began to realize that he was completely outmatched, and decided to use her fear of blood to his advantage, slitting his wrists to paralyse her. As Kabuto began to beat on Tsunade, Shizune and Naruto came to her rescue. While both were easily defeated, Naruto was able to overcome his injuries and continued to protect Tsunade. Although Tsunade told him to run, Naruto refused, and managed to hit Kabuto with a perfected Rasengan in his effort to protect her, defeating Kabuto. As Naruto collapsed, and was left near death due to Kabuto's last attack, Tsunade rushed to his aid and attempted to heal him, not willing to allow him to die. Her efforts were successful, and Naruto claimed the amulet he had now won before losing consciousness. Putting the necklace around his neck, Tsunade asked once more for its wearer to become Hokage.

Orochimaru, worrying about what kind of threat Naruto might become when he got older, tried to kill him, though Tsunade blocked that attack, using herself as a human shield. Orochimaru inquired as to why she was protecting Naruto, to which she replied that Naruto would someday be Hokage, and that she would not allow him to die before that happened. With that, Tsunade accepted the title of Fifth Hokage that she had been offered, and overcame her fear of blood, her first action being to eliminate Orochimaru. Joining forces with the still drugged Jiraiya, the two attacked Orochimaru. After a battle of summons, Tsunade dealt the finishing blow to Orochimaru. Defeated, Orochimaru escaped, vowing to destroy Konoha once he'd healed himself. Once Naruto recovered, the group returned to Konoha, Tsunade ready to take the role Dan and Nawaki so dearly desired, and secretly believing that Naruto would someday become a great Hokage. Also, like with Nawaki and Dan before Naruto, Tsunade gives him a kiss on the forehead to show her faith in him.

Sasuke Retrieval Arc
Soon after arriving in Konoha to take her place as Hokage, Tsunade healed the mental injuries inflicted by Itachi Uchiha's Tsukuyomi on Kakashi Hatake and Sasuke Uchiha. She also gave a grim prognosis on Rock Lee's condition. She stated that the only procedure that could allow him to return to duty as a shinobi was one that she alone was capable of performing, and it only had a fifty per cent chance of success; if it didn't succeed then it would prove to be fatal for Lee.

Not liking the odds of such a dangerous procedure, Tsunade advised Lee that it was best that he retire as a shinobi and find another profession. In the anime, while Lee is struggling to decide what he should do, Tsunade looks into ways to improve his chance of survival. Thinking back to how she had seen Kabuto withstand Naruto's Rasengan, Tsunade used Kabuto's technique as an inspiration to expand on the life-threatening operation and improved Lee's chances of survival from fifty per cent to fifty-eight per cent. Lee finally agreed to undergo the procedure and survives.

When Sasuke defected from the village so that he could go to Orochimaru, Tsunade was forced to send out a group of Genin to try and stop and retrieve him. She also used Konoha's reacquired alliance with Sunagakure to call in a favour for reinforcements, hoping to give the retrieval team some back-up. Despite her efforts, the group ultimately failed, and Tsunade helped in healing their fatal injuries, bringing them back to full health. She was particularly instrumental in the healing of Chōji, mixing the antidote to the side effects of the Three Coloured Pills that she got from the medical encyclopaedia kept by the Naras; a fact Chōza gratefully stated. In the aftermath of Sasuke's betrayal, Sakura Haruno asked to become Tsunade's apprentice, which Tsunade gladly accepted.

Pre-Shippūden Filler Arcs
Tsunade appeared in numerous filler arcs, though she typically did nothing more than sending others out on missions, occasionally trying new ways of deciding who would go on a specific mission. Her goal during the filler arcs was to keep Naruto busy until Jiraiya came back, to prevent him from going after Sasuke himself. When the Legendary Stupid Brothers escape from prison, she convinces them to surrender with a quick display of genjutsu and her strength. In another filler, she summoned Katsuyu to deal with some impersonators of Rock Lee and Might Guy, who had entered the village.

Part II
After Naruto's return to Konoha after the time-skip, the village's elders questioned Tsunade's decision to allow Naruto to go out on missions when Akatsuki sought to capture him. As such, the elders forced Tsunade to allow one of the men of Danzō Shimura, a fierce opponent of the Third Hokage, to be teamed with Naruto. Not trusting Danzō, Tsunade assigned Yamato to lead Naruto, and to keep an eye on Danzō's addition to the team, Sai.

Hidan and Kakuzu Arc
Later, when two Akatsuki members entered the Land of Fire - namely Hidan and Kakuzu - Tsunade mobilized the Nijū Shōtai to look for and if possible, capture the Akatsuki duo. While capture never came to be possible, the Akatsuki members were both defeated. Tsunade later performed an autopsy on Kakuzu, and found Naruto's newest technique, Wind Release: Rasenshuriken to be too dangerous for use, based on the damage done to Kakuzu's body and Naruto's arm. She explained that the attack had struck at a cellular level, causing extensive damage to the both of them, and regretfully told Kakashi and Yamato not to allow Naruto to use the technique again.

Three-Tails Arc
In the anime, after finishing her autopsy on Kakuzu, Tsunade received a report from a deceased ANBU captain about Orochimaru and Sasuke's whereabouts. She called for Kakashi, and put him in charge of Team 8 to investigate. Because the mission involved a chance of finding Sasuke, Tsunade tried to keep Naruto from finding out about it. He found out anyway, so Tsunade didn't hesitate to send him as back-up.

Later, Tsunade received news that Team Kakashi had encountered the Three-Tails. Deciding that they needed to capture the beast quickly, as to not let it fall into enemy hands, Tsunade ordered Tenten, Rock Lee, and Ino Yamanaka to aid Team Kakashi in sealing the beast. Before sending them out, Tsunade made a large and special scroll to aid the team in sealing the beast. She also decided to summon and send out Katsuyu for further assistance. When the forces they sent continued to have problems with the sealing, Tsunade called them back to Konoha, and sent some ANBU to replace them. After she heard about the ANBU losing contact with Konoha, and the disappearance of the Three-Tails, Tsunade suspected that Akatsuki were somehow involved.

Tsuchigumo Kinjutsu Arc
In the anime, word reaches Konoha that the Tsuchigumo clan's fort protecting a powerful forbidden technique was under attack. With Team Kakashi and Team Kurenai being the closest, Tsunade sent Katsuyu to inform them of their mission to aid the Tsuchigumo clan, in accordance with the peace treaty the Third Hokage made with them. Tsunade later receives word from the teams that they and the clan have considered destroying the technique to end the possible danger it can cause.

Invasion of Pain Arc
When word reaches Konoha of Jiraiya's death, Tsunade makes the village's top priority analyzing the clues Jiraiya left behind about Pain's identity. While the likes of Shizune, Ibiki, and Shikamaru are hard at work, Tsunade allows herself an opportunity to cry for her old friend. Naruto, just as badly affected by Jiraiya's death as Tsunade, went away to train, both of them knowing that he was Pain's next target.

When the invasion of Pain began, Tsunade tried to send word for Naruto to return home. She was stopped by the Konoha Council, who feared his capture by Akatsuki. However, Tsunade insisted that they must have faith in Naruto, along with the rest of the next generation, and so they relented. Tsunade began issuing orders for the village's defence, placing extra protection around those still working on Pain's secret. She summoned Katsuyu, and had her divide and seek out every villager so that she could protect and heal them remotely.

While sitting in the middle of a seal guarded by ANBU, transferring her chakra to Katsuyu, she was found by Pain's Deva Path, whom she recognized as one of the orphans Jiraiya trained in the past. Tsunade refused to tell it where Naruto was, proclaiming that Akatsuki was just a terrorist group. When Pain discovered Naruto's location through other means, the Deva Path resolved to make Tsunade see what Akatsuki's true goals were.

The Deva Path destroys the village. In the few moments between when the destruction began and ended, Tsunade poured all her chakra into Katsuyu in order to keep the inhabitants safe. In the aftermath, she confronted Pain, who attempted to kill her with his Asura Path. It was stopped by Naruto, who informed Tsunade that he would personally deal with Pain. Having used up almost all of her chakra, Tsunade's elderly form resurfaced, she then falls into a coma and does not see Naruto's victory over Pain.

Confining the Jinchūriki Arc
While Tsunade remained in a comatose state, Danzō was chosen to replace her as the Candidate Sixth Hokage. However, he was killed by the now-international criminal Sasuke Uchiha after the Kage Summit and the village prepared to make Kakashi Hatake the new Hokage, but Tsunade woke up before the appointment could be finalised. Tsunade learned of everything that happened while she was in her coma; the start of the Fourth Shinobi World War, the Shinobi Alliance, and the identity of Tobi. After replenishing her chakra levels, she convened a war council to prepare the village for the impending war.

Three days later, Tsunade goes to Kumogakure to meet with the other heads of the Alliance. She is warmly greeted by the Fifth Mizukage while the Third Tsuchikage suggests she retire so that she can finish recuperating. When they get down to business, Tsunade learns that the other Kage have decided to send Naruto and Killer B into hiding to keep them safe from Akatsuki. Tsunade argues against this, believing that the jinchūriki will be valuable assets in the coming war. The other Kage insist that it's for the best and the Fifth Kazekage reminds her that she must think in the interest of all the countries, not just Konoha. She agrees with their decision and later helps organise the joint armies, placing particular interest in the Logistical Support and Medical Division and the Intelligence Division.

Shinobi World War Arc
Tsunade remains at headquarters with the Tsuchikage and Fourth Raikage, providing input when needed. When the First Division engages several revived shinobi, Tsunade is disturbed by the possibility that Dan may be among their numbers. She is later surprised by news of the Gold and Silver Brothers' Nine-Tails chakra.

When news reaches headquarters of Naruto and B's escape from their confinement, the Raikage asks Tsunade to help him deal with them. She summons Katsuyu and leaves it at headquarters, taking a mini-Katsuyu with her so that she and the Raikage can keep up to date on any urgent matters. When they intercept Naruto and B, Tsunade is amazed by Naruto's Nine-Tails Chakra Mode. Naruto appeals to Tsunade to let him and B pass, but she informs him that she can no longer show him special treatment and must do what is best for the Alliance. Naruto tries to escape but is stopped by the Raikage, who voices his willingness to kill Naruto and B if they would not submit. Tsunade however, tells him that she will not allow him to do so.

Remembering Naruto's words, that he would not die until he became the Hokage, she argues that even if Naruto being killed delayed the enemy's plan, that it's unlikely that another jinchūriki will have the same success as Naruto has had with controlling the Nine-Tails, and going against A's instructions, allows him to pass through. When it seems that A will not be swayed, Tsunade is intent on fighting him, but as it turns out, A was testing Naruto and agrees to let him continue on to the battlefield when he proves himself.

Upon returning to headquarters, Tsunade reviews the data from the medical team and is disconcerted by what Madara Uchiha and Orochimaru had achieved with her grandfather's cells, and concludes that harvesting them is what had allowed Madara to live for so long. When A asks if there are any hints on how to defeat Madara, Tsunade replies by saying that Madara may in fact be the true definition of the word "immortal". She then tells Shikaku to inform Naruto and B about White Zetsu's transformation ability.

Creation and conception
Tsunade's name is taken from the character of the same name from. The Tsunade in that story is vastly different in terms of personality, along with the fact that unlike her manga counterpart the original Tsunade was married to Jiraiya, however both were known to greatly excel in slug magic.

Trivia

 * The name means "mooring rope".
 * Tsunade shares the same blood type with her former team-mates, Jiraiya and Orochimaru.
 * Tsunade was the first female Hokage, as well as the first female Kage that appeared in the series.
 * Tsunade is first mentioned when Might Guy questions Rock Lee, Neji, and Tenten about their goals as Genin. Tenten says that she wants to become a great kunoichi and follow the footsteps of the legendary Tsunade.
 * According to the Naruto databook:
 * Tsunade's hobby is gambling.
 * Tsunade wishes to fight Naruto.
 * 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.
 * While Tsunade's English anime voice actor is Debi Mae West, in most games she is voiced by Mary Elizabeth McGlynn, who is Kurenai Yūhi's voice actor. The few games where she is voiced by her anime voice actor are Naruto Shippūden: Legends: Akatsuki Rising, Naruto: Uzumaki Chronicles 2, Naruto: Clash of Ninja Revolution, and Naruto Shippūden: Clash of Ninja Revolution 3. In Naruto: Clash of Ninja Revolution 2, while being voiced by Mary Elizabeth McGlynn throughout the story-line, during game-play, most of Debi Mae West's voice-overs from the first game are still used.
 * Tsunade's grandmother, Mito Uzumaki had a similar diamond shape mark on her forehead. It is possible that Tsunade modelled her own seal after this.

Quotes

 * (When about to fight Naruto) "One of the Legendary Sannin taking on a snot-nosed genin… I oughta be ashamed of myself."
 * (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 Orochimaru) "Why am I putting my life on the line? Because now… I am the Fifth Hokage of the Village Hidden in the Leaves!"
 * (To Orochimaru about Naruto) "I will die before I let you touch him!"
 * (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 advisers) "People like Jiraiya… and Sarutobi, and Elder Chiyo of the Sand 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 Shizune) "People become stronger because there are memories that they will not forget."