Chev Chelios (Jason Statham) is a Los Angeles-based British hitman, working for a crime syndicate headed by Carlito (Carlos Sanz). Chelios is contracted by Carlito to kill mafia boss Don Kim (Keone Young) as members of the Triads have been encroaching on Carlito's business. Chelios goes to Don Kim and apparently murders him.
However, Ricky Verona (Jose Pablo Cantillo), an ambitious small-time criminal uses the opportunity to conspire with Carlito against Chelios; Verona will kill Chelios so the Triads do not retaliate, and then take Chelios's place as Carlito's new hired gun. The morning after Don Kim's death, while Chelios sleeps in his apartment, Verona, his brother Alex (Jay Xcala), and several henchmen break in and inject Chelios with a Chinese synthetic drug which inhibits the flow of adrenaline, slowing the heart and eventually killing the victim. Chelios wakes to find a recording left by Verona showing what he has done. In anger, Chelios smashes his TV and heads out.
Chelios phones Mafia surgeon Doc Miles (Dwight Yoakam), who informs Chelios that in order to survive he must keep his adrenaline pumping through constant excitement and danger, and he is unsure if the antidote exists. Chelios keeps his adrenaline up through reckless and dangerous acts like picking fights with other gangsters, taking illegal drugs and synthetic epinephrine, fighting with police, stealing a police officer's motorcycle, having public sex with his girlfriend Eve (Amy Smart), and driving his car through a shopping mall.
Chelios visits Carlito at his penthouse and asks him to help find an antidote, as well as to find and kill Verona and his crew. Carlito says there is no antidote and only confirms that Carlito and Verona are working together. Carlito tells Chelios how he will use his death as a scapegoat against the Chinese. An angered Chelios leaves Carlito's penthouse to find Verona. Through Chelios' street contact, a transvestite named Kaylo (Efren Ramirez), he finds Alex at a restaurant and unsuccessfully interrogates him about his brother's whereabouts before killing him. Chelios phones Verona through Alex's phone and tells him of his brother's death, prompting Verona to send thugs after Eve as a revenge. Chelios rushes to pick up Eve before Verona's thugs get to her. Chelios reveals his true profession to her and that he was planning to retire to spend more time with her.
Kaylo, who has been kidnapped by Carlito's men, is forced to call Chelios and tell him that Verona is at a Triad warehouse. Chelios goes there, finding Kaylo's corpse and the henchmen. They reveal that Carlito ordered them to kill Chelios. Eve, who has followed Chelios, unexpectedly arrives, but then escapes with Chelios after a shootout with Carlito's henchmen. Chelios and Eve go to Doc Miles's place, where Miles explains that he cannot cure Chelios. Knowing that he will die soon, Chelios decides to take his revenge on Verona and arranges a meeting with him at a downtown hotel.
Chelios goes to the rooftop of the hotel and meets with Verona, Carlito, and his henchmen. Carlito takes out a syringe, filled with the same poison used by Verona. As he is about to kill Chelios by injecting the second dose into him, Don Kim, revealed to be alive as Chelios spared him, arrives with his Triads to assist Chelios and a shootout follows. During the battle, several of Don Kim's and all of Carlito's men are killed. Carlito tries to escape with his private helicopter, but Chelios manages to catch up to him and holds him at gunpoint. Before Chelios can kill Carlito, Verona sneaks behind and injects Chelios with the syringe, after which Chelios collapses. Carlito himself is betrayed by Verona, who shoots him to death and then tries to escape with his helicopter.
Chelios manages to stand up, boards the helicopter, and engages in a fight with Verona. After some struggle, Chelios manages to pull Verona out of the helicopter and while mid-air, Chelios proceeds to snap Verona's neck, killing him. While falling, Chelios calls Eve on his cell phone to apologize for not coming back. Chelios hits a car, bounces off it and lands right in front of the camera. In the last shot, it is implied that his adrenaline is indeed still flowing fast; his nostrils flare, he blinks, and two heartbeats are heard.
Output: Which twist is revealed right before Chelios will be injected with a second dose of the drug?