Sunita (Jiah Khan) is a medical student, working on a project about the human brain with her class friend. When she is denied access by her professor to the curious case of Sanjay Singhania (Aamir Khan), a man reported to have anterograde amnesia, because it is under criminal investigation, Sunita decides to investigate the matter herself.
It is revealed that Sanjay loses his memory every 15 minutes. He uses a system of photographs, notes, and tattoos on his body to recover his memory after each cycle to remind himself of his mission: to avenge the death of his beloved Kalpana (Asin). He systematically kills the people who were tied to the murder. His main target is Ghajini Dharmatma (Pradeep Rawat), a notable social personality in the city, and the man directly responsible for Kalpana’s death and Sanjay’s condition.