Known for its Space Western theme, Trigun is about a man named "Vash the Stampede" and the two Bernardelli Insurance Society employees who follow him around in order to minimize the damages inevitably caused by his appearance. Most of the damage attributed to Vash is actually caused by bounty hunters in pursuit of the "60,000,000,000$$" (sixty billion "double dollars") bounty on Vash's head for the destruction of the city of July. However, he cannot remember the incident clearly due to his amnesia. Throughout his travels, Vash tries to save lives using non-lethal force. He is occasionally joined by a priest, Nicholas D. Wolfwood, who, like Vash, is a superb gunfighter.
As the series progresses, more is gradually learned about Vash's mysterious history and the history of human civilization on the planet Gunsmoke. The series often employs comic relief and is mostly light-hearted in tone, although the tone shifts toward darker and more dramatic situations as it draws to a conclusion. It also involves moral conflict pertaining to the morality of killing other living things, even when justified (i.e. self-defense/defending others).