Tsunade is the Fifth Hokage 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".
Tsunade typically projects a tough demeanour, even when facing great personal difficulty. She readily criticizes others for their faults, such as Naruto for his immaturity, or Jiraiya for his perversion, though her habits are rarely any better. Tsunade however does show sympathy for others from time to time, 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 ninja. She also allowed herself to cry when she learned of Jiraiya's death, though not in public.
When first introduced, Tsunade is 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 Dan and Nawaki. She has a change of heart, puts her faith in Naruto, and takes 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 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 ninja and should be used by the village as any other ninja would be.
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 "The Legendary Sucker" (伝説のカモ, Densetsu no Kamo) 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, 賭 (kake), means "gamble", or "wager", as gambling is one of her favourite pastimes.
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.
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.
Despite the fact that Tsunade shuns all of Jiraiya's romantic advances throughout most of the storyline, she still considered him her friend despite his nature. 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 good friend. She is now the last of the Sannin. Tsunade took Shizune as an apprentice and trusts her greatly. In fact, Shizune is one of the few people Tsunade trusts with absolute certainty. Tsunade also owns a pet pig, Tonton which she leaves mostly to Shizune's care. Beneath all of this tough exterior is a woman that truly loves her village and its people.
- Tsunade and Shizune make their first appearance in the Sonic Adventure Series in "Sonic's Adventures of Naruto Shippuden the Movie"
- Tsunade makes a cameo in "Sonic's Adventures of Teenage Mutant Ninja Turtles" as she ask Naruto, Hinata, Sakura, Koyuki and Dororo to find an old friend of hers called Hamato Yoshi