Dismissed by those around him as a miserable loser, Arata Kaizaki, 27, bounces back and forth from one work to another after leaving his first company. His unremarkable childhood takes a sudden turn when he encounters Ryou Yoake, a founder of the ReLife Research Institute who, with the aid of a magical drug, gives Arata a chance to improve his life for the better. Taking it with no second glance, the next day Arata wakes up to notice that his face has reverted to that of a 17-year-old.
Arata soon discovers that he is now the target of a special trial and is expected to enter high school as a one-year transfer student. While he initially thinks it would be a cinch because of his superior life knowledge, on his first day, Arata appears to be terribly wrong: he flunks all his exams, is totally out of shape, and can not keep up with the latest school reforms that have arisen over the last 10 years. In addition to this, Ryou was appointed to watch him, adding constant irritation to Arata. ReLIFE explores Arata's attempt to adjust to his hectic new environment and stop committing his previous errors, all while gradually finding out more about his classmates.