The film opens with Sunita (Jiah khan), a medical student, and her friends working on a project about the human brain. She wants to investigate the curious case of Sanjay Singhania (Aamir Khan), a (former) notable city businessman, who is reported to have anterograde amnesia. Her professor denies access to Sanjay's records as it is currently under criminal investigation. Sunita nonetheless decides to investigate the matter herself.

The story goes forward through flashback as Sunita reads Sanjay's diary between 2005 and 2006. The flashback starts with Sanjay Singhania, who is a successful businessman and owner of Air Voice company .Sanjay sends his men to put up an ad on an apartment. Kalpana (Asin Thottumkal), a struggling model, is the resident of this apartment. She takes up the offer in the hope of developing her career through it. Sanjay and Kalpana meet and Kalpana decides to act as Sanjay Singhania's girlfriend for fame and to boost her career. Sanjay introduces himself as Sachin, a normal guy looking for a job. Soon Kalpana and Sanjay begin falling in love with each other. Sanjay proposes to herwill tell her his true identity or he will leave. Kalpana accepts his proposal. After that, the diary comes to an abrupt stop. While flipping through the pages, Sunita reads about how Kalpana found out about a prostitution racket wherein small girls were being transported to Goa for the purpose by Ghajini, an important member of the society but is actually a gang honcho. Kalpana saves the girls and this angers Ghajini. He sets out to murder Kalpana, who had ruined his plans. Sanjay was also there by coincidence and witnessed the incident of Kalpana's brutal murder. Seconds later, his head was hit by a heavy iron rod. This injury caused his anterograde amnesia which persisted. Sunita had previously warned Ghajini about the danger he faced from Sanjay and Ghajini had scratched out all of Sanjay's tattoos and destroyed all proof against him. But when Sunita comes to know his reality, she decided to help Sanjay. With her help, Sanjay is able to kill Ghajini and his henchmen thus avenging the death of Kalpana. The film ends on a happy note where Sanjay is seen in an orphanage and Sunita gifts him the cement slab of plaster on which Kalpana and Sanjay had pressed their feet on to mark their entry into a new apartment.