Frank Martin (Jason Statham) has relocated from southern France, to Miami, Florida, where he is driving for the wealthy Billings family, headed by Jefferson Billings (Matthew Modine). Frank has unexpectedly bonded with the Billings' son, Jack (Hunter Clary), whom he drives to and from elementary school in his new Audi A8 W12[2]. Frank is also preparing for the arrival of Inspector Tarconi (François Berléand), his detective friend from France, who has come to spend his holiday in Florida with Frank.
Frank takes Jack to a doctor's checkup, only to be ambushed by a gang of ruthless criminals dressed as doctors who are attempting to inject Jack with a deadly virus. A lengthy fight erupts between the armed villainess Lola (Kate Nauta) and the unarmed Frank; nevertheless, Frank is able to escape with Jack. Frank drives back to Jack's house, but Lola arrives and forces her way into his car when he is held at a standoff by an unseen sniper capable of penetrating the car's bulletproof glass. Frank then drives Lola and Jack away from oncoming police units in a long chase sequence.
They arrive at a warehouse occupied by a gang led by Gianni (Alessandro Gassman), the Italian antagonist and ringleader of the operation. Frank is forced to leave Jack in the hands of Gianni and his gang. While leaving the warehouse, he discovers an explosive attached to the car and succeeds in removing it prior to detonation. Jack is later returned to his family after the payment of a ransom, but unknown to them and Frank, Jack has been infected with a deadly virus that will eventually kill anyone that comes into contact with it "within a span of 48 hours".
Frank decides to take matters into his own hands and finds one of the fake doctors that kidnapped Jack and pretends to infect the Russian henchman, Dimitri (Jason Flemyng), with the same virus (was actually water in that syringe). Dimitri panics and hurries to his lab to get the cure, but Frank follows him and takes the antidote from him. After disposing of Dimitri, Frank faces the doctor in charge of the lab. The doctor hurls the only two vials containing the antidote out of the window and Frank quickly jumps to catch them. He lands on a car and catches one, only to find it broken. He saves the other vial from being run over by a truck. Frank sneaks back into The Billings' home and explains his innocence to Audrey (Amber Valletta), the only one who trusts him. Jack is cured, but he had already breathed on his mother and his father, who is the director of National Drug Control Policy. Jack's father is taking part of a major conference which brings together the heads of many anti-drug organizations from around the world. Frank learns that, through Jack's infected father, a Colombian drug cartel wishes to infect and kill all of the conference attendees so that the cartel's cocaine-smuggling business can operate without interference.
Frank drives to the henchman-garrisoned house of Gianni, who has already injected himself with the remaining supply of antidote to hide it from capture. Following a fight in the garage and another one in which he uses a firehose to fight off the villains, Frank finds Gianni and holds him at gunpoint, but Lola shows up. Leaving Lola to deal with Frank, Gianni flees the scene. A final, yet brief, fight ensues between the both of them with Frank emerging as the victor, and Lola killed.
Frank then follows Gianni, who is making an escape in his helicopter to a waiting jet at the airport. Using a Lamborghini Murcielago 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, leaving the Lamborghini to collide with a sign at the end of the runway. The explosion damages the aircraft's landing gear. Frank gets into the interior of the plane through the open wheel well. When the copilot comes to investigate the damaged landing gear, Frank breaks his neck, then he quickly confronts Gianni, who pulls a gun on him. Frank thwarts his attempt to fire the weapon, and they begin wrestling for the gun. Gianni is able to take a shot at Frank, who narrowly dodges the bullet. The round hits the pilot and the plane eventually crashes into the ocean.
Gianni tries to strangle Frank, but Frank manages to break Gianni's spine with his elbow, rendering Gianni alive but immobile. Frank then pushes his captive and himself out of the sinking plane. On the ocean's surface, police teams arrive. The Billings have been given the antidote, and Frank goes to visit them in the hospital. Before entering their room, he sees them with Jack, who is joking with them, and he silently walks back to his car where Tarconi is waiting. He drops his friend at the airport. Alone, Frank is about to drive away when he receives a call from a man who needs a transporter.
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