In mid-2000s, the illegal drug trade based in Kuala Lumpur is booming. The Malaysian authorities are called upon for assistance by their Indian counterparts. The Indian team sent to Kuala Lumpur is headed by Deputy Commissioner of Police D'Silva (Boman Irani), who targets the illegal drug operations of Singhania. Helping him along the way is Inspector Vishal Malik (Om Puri), an Indian officer from Interpol. Both of them know that in order to put an end to the illegal drug trade, they must capture "Don" (Shah Rukh Khan) who manages Singhania's business in Kuala Lumpur. Singhania was one of the two closest and most trusted men of Boris, a criminal who, during his lifetime, went underground and was presumed dead by the police. Boris's other lieutenant was a man called Vardhan, equally ruthless as Singhania, but his whereabouts have not surfaced recently. The police thinks that Singhania had killed Vardhan when Boris was about to hand over his drug business to Vardhan.

Don is extremely dangerous - he has even been known to murdered one of his close associate Ramesh, who attempted to leave the cartel. Ramesh's future wife Kamini (Kareena Kapoor) decides to help the police arrest Don but in the process, she is also killed. Now, Ramesh's sister Roma (Priyanka Chopra) manages to get her way into Don's gang - her real plan is to murder Don in order to avenge her brother and his fiancé.

Don and his inner circle, consisting of Anita (Isha Koppikar) and Narang (Pawan Malhotra) travel to India for a cocaine transaction. An Indian police team led by D'Silva follow them there and capture Don who is fatally injured while trying to flee from police. D'Silva keeps this a secret from the department and media as he decides to track down an exact look-alike of Don named Vijay (also Shah Rukh Khan) from Mumbai and asks him to pose as Don so the police can get to Singhania. Vijay agrees when D'Silva promises to admit Deepu (Tanay Chheda), a kid Vijay looks after, to a school in Kuala Lumpur.

Meanwhile, Jasjit (Arjun Rampal), Deepu's father has just been released from prison and becomes bent on killing DCP D'Silva. This is because Jasjit was committing a crime in order to save his family from a gang of criminals and D'Silva had Jasjit [a low level officer in Mumbai police at the time] arrested, thereby preventing Jasjit from saving his wife from death. Jasjit also does not know what happened to his son after he went to prison.

Vijay is admitted to the same hospital as Don by D'Silva. Vijay soon gets all the scars and marks which Don has on his body. Suddenly, Don dies of heart failure and the masquerade becomes inevitable. When Vijay (as Don) re-enters the gang in Kuala Lumpur, he will have lost his memory—the more he learns about Don, the more he shall remember. Don has a disc which contains some of their most vital information about deals and contacts. Vijay agrees to take this disc to D'Silva - Roma (who is now a close associate of Don) decides to accompany him. When they arrive, Roma attempts to kill Vijay (assuming he is Don). However, DCP D'Silva intervenes and tells Roma about his secret plan to reach to Singhania. Roma decides help the police to capture Singhania and joins their plan.

Singhania comes to Kuala Lumpur for meeting with his clients. There DCP D'Silva murders him by adding poison to his drinks. Suddenly, the Malaysian police and Interpol arrives at the hotel. Vijay and the core gang members are all arrested by Interpol. D'Silva is apparently killed in shoot-out - this is unfortunate for Vijay because D'Silva is the only person who could prove that Vijay is not the real Don. Now Don's inner circle also turns against Vijay of knowing his true identity. Vijay escapes from police custody and tries to pursue the disc he gave to D'Silva in order to prove his innocence.

Jasjit secretly enters into DCP D'Silva's flat in Kuala Lumpur and waits for him with a gun. There he finds the disc Vijay gave to DCP and is shocked by the contents of it. He soon receives a phone-call saying that if he wants to see his son again, he will have to bring the disc to the men who have Deepu hostage. At this meeting, it is revealed that DCP D'Silva was alive all along and is actually Vardhan, the other lieutenant of Boris. Jasjit somehow manages to escape with his son from the smugglers. He meets Vijay [now at large] and Roma and reveals that D'Silva is really Vardhan - the three hatch a plot to help Interpol arrest Vardhan. The next day, Jasjit arranges a meeting with Vardhan in Langkawi, saying he will hand over the disc. The trio informs the Malaysian police and Interpol about the meeting and gets Vardhan arrested. Vijay gets badly injured during the final hand-to-hand combat with Vardhan, and is rushed to hospital - before he leaves, Roma confesses her love for him. In a final twist, it is revealed that the real Don is alive and was pretending to be Vijay the whole time. In the hospital, Don quickly recovered from the injury and overheard DCP D'Silva's conversation with Vijay. After Vijay's operation, Don got up from the room while D'Silva and Ashok aren't in site and went to the room where Vijay lay. He removed and switced places with Vijay and added poison meaning Vijay died of heart failiure, not Don. It is also revealed that the disc Don gave to the police was fake. Now with both Vardhan and Singhania removed from his path, Don becomes the master of entire Asian drug dealings.

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