Frank Martin (Jason Statham) has relocated from southern France to Miami, Florida. As a favor, he becomes a temporary chauffeur for the wealthy Billings family. The marriage of Jefferson (Matthew Modine) and Audrey Billings (Amber Valletta) is under great strain due to the demands of his high-profile government job. Frank bonds with their son, Jack (Hunter Clary), whom he drives to and from elementary school in his new Audi A8 W12.[2] Later, a somewhat drunk Audrey shows up at Frank's home and tries to seduce him, but he tactfully sends her home.
When Frank takes Jack for a medical checkup, he realizes barely in time that impostors have killed and replaced the doctor and receptionist. A lengthy fight erupts between villains, led by Lola (Kate Nauta), and the unarmed Frank; which results in the death of one of the doctors. Frank escapes with Jack. Just as they arrive at Jack's house, he receives a phone call. The caller informs him that he and Jack are in the sights of a sniper capable of penetrating the car's bulletproof glass. Frank is forced to let Lola into the car; they speed away with Jack, shaking off many pursuing police cars.
They arrive at a warehouse, where Frank meets Gianni (Alessandro Gassman), the ringleader of the operation. Frank is ordered to leave without Jack. He discovers an explosive attached to the car and succeeds in removing it prior to detonation. Jack is returned to his family after the payment of a ransom, but unknown to them and Frank, Jack has been injected with a deadly virus that will eventually kill anyone who the child breathes on.
Suspected by everyone except Audrey of being one of the kidnappers, Frank tracks down the remaining fake doctor, Dimitri (Jason Flemyng), with Tarconi's assistance. Frank pretends to infect Dimitri with the same virus, then lets him escape. Dimitri panics and hurries to a lab to get the cure, with Frank following behind. In his panic, Dimitri kills Tipov, another of Gianni's men, in his attempt to force the scientist in charge of the lab to give him the cure. Frank arrives and kills first another henchman, then Dimitri (after revealing the Dimitri wasn't infected after all); but when Frank refuses to bargain with him, the scientist hurls the only two vials containing the antidote out of the window into traffic. Frank manages to retrieve only one vial intact.
Frank sneaks back into the Billings home and tells an already ailing Audrey what is happening. He uses the antidote on Jack. Meanwhile, a coughing Jefferson, the director of National Drug Control Policy, addresses the heads of many anti-drug organizations from around the world at a conference; infecting all of them in the process.
Frank drives to the house of Gianni, who has decided to inject himself with the remaining supply of antidote as a precaution. After dispatching Gianni's many henchmen, Frank has the archvillain at gunpoint. Gianni explains that a Colombian drug cartel is paying him to get rid of its enemies; and that Frank cannot risk killing him, for his death would render the antidote unusable. An armed Lola shows up, leading to a standoff. Gianni leaves Lola to deal with Frank; which results in Frank finally killing her by kicking her into a wine rack with sharp metal points.
Frank tracks Gianni, who is making an escape in his helicopter to a waiting jet. Using a Lamborghini Murcielago Roadster from Gianni's garage, Frank speeds to the airport and boards Gianni's jet by driving onto the runway and climbing onto the jet's nose gear. After killing the co-pilot; Frank gets into the interior of the plane and confronts Gianni, who pulls a gun on him. When they wrestle for it, a round kills the pilot and the plane crashes into the ocean. Frank incapacitates Gianni by paralyzing him (rendering him immobile while preserving the antidote in his system), then pushes his captive and himself out of the sinking plane. Boats converge to pick them up.
The Billings are given the antidote. When Frank visits them in the hospital, before entering their room, he sees them with Jack, who is joking with them. He silently walks back to his car, where Tarconi is waiting. He drops his friend at the airport. Alone, Frank receives a call from a man who needs a transporter.