The bosses of the European drug cartel meet in the French Riviera to discuss a new threat emerging from Asia. Don (Shahrukh Khan) is jeopardizing their business because he is able to sell drugs at a much lower price to their customers. The bosses send word out that Don must die. Don has been living in Thailand for the past five years and goes to a remote settlement to pick up a shipment of cocaine. Instead of a normal transaction, Don has to fight his way out because the more powerful European dealers want him dead. He then inexplicable goes back to Malaysia where he surrenders to Roma (Priyanka Chopra) and Inspector Malik (Om Puri). Don is sentenced to death and sent to a Malaysian prison where he meets his old rival Vardhaan (Boman Irani). Don and Vardhaan escape the prison by poisoning all the inmates and go to Zurich, Switzerland, where Don meets his girlfriend and trusted companion, Ayesha (Lara Dutta). In Zurich, they retrieve the contents of a locker only Vardhaan could access. The locker holds a tape that shows Diwan (Aly Khan), the vice president of a Euro printing bank called the DZB, bribing someone to kill a competitor. Don blackmails Diwan into giving him the blueprints to the bank so that he can steal the printing plates. Diwan gives him fake information and hires assassins instead. Don manages to escape and forces the assassins to work for him. Diwan, left with no choice, hands over the real information.
Don and his new team plan a bank robbery and carry out their plan by taking hostages. After stealing the printing plates, Don is betrayed by Vardhaan and his team but manages to escape. However, one of the members, Sameer (Kunal Kapoor), calls the police and Don is captured. Unable to enter the bank and free the hostages, the police are forced to work with Don to get back into the bank in exchange for immunity. Don and Roma manage to reach Vardhaan but Roma is shot because she refuses to kill Don when told to do so. This gives an idea that Roma still has soft corner for Don. Don, Vardhaan and his thugs fight and Don manages to defeat them. He then get his immunity papers and takes Roma to an ambulance. Don and Roma exchange one glance at each other before the ambulance doors close. He then detonates a bomb he planted earlier in Diwan’s car. It is revealed that Don actually still has the original money plates and gave fake ones to the police. The fake plates are destroyed in the explosion that kills Diwan. The police cannot do anything as Don has immunity and do not know that Don has the real plates. Don also gives the police a disc of all his associates but it is really a disc with the names of the European drug cartel. All the members of the cartel are arrested and Don becomes the king of the European underworld.