Tsukuyomi is noted to be one of the most powerful genjutsu in existence. It is said to represent the "Spiritual World and Darkness" (精神界と闇, Seishinkai to Yami), the antipode to Amaterasu — a ninjutsu of similar power.
Tsukuyomi requires eye contact to be performed, trapping the target within an illusion completely under the user's control. Itachi's prowess with the technique has allowed him to alter the perception of time with ease within the genjutsu to make a few seconds seem like many days as a means to torture the target. This results in the victim suffering psychological trauma that incapacitates them for a considerable period of time. After Itachi used it on Kakashi in Part I, Kisame was surprised that Kakashi's mind was still intact. Only Tsunade has been shown capable of curing this psychological damage.
In the anime during Part I, Itachi's use of Tsukuyomi typically featured a red moon casting a red light throughout the illusion with a cloudy atmosphere, giving the background a blood-red appearance while the victim within the illusion is in depicted in an inverted grey scale.
Such a powerful technique is not without its disadvantages however. Due to the complexity of the illusion and the quickness with which it is executed, an enormous amount of chakra is necessary and an added amount of stress is placed on the left eye, leaving Itachi's vision more blurred. Before using it on Kakashi in Part I, Itachi stated that Tsukuyomi can only be broken by a Sharingan user that shares the same blood as him; as demonstrated when Sasuke overcame Itachi's Tsukuyomi in their battle.
Pulling from the ancient Japanese myth of Amaterasu, Tsukuyomi, and Susanoo, where when Izanagi washed his face after escaping the underworld his left eye became Tsukuyomi, the Moon god. Interestingly, as Tsukuyomi is the Moon, he is also associated with the passing of time, and at times cited to be the God of Time (or at least of the calendar), fitting the genjutsu's ability to alter the perception of the passing of time.
- In Naruto: Ultimate Ninja Storm, Itachi uses Tsukuyomi in a different manner. He has the red moon crush the opponent while the image of the moon warps into a copy of his Mangekyō Sharingan eye.
- In a novel, Itachi uses this technique to kill Izumi Uchiha, despite one of the limitations of genjutsu in the series that it can't kill the target on its own.