In 2017, humans live in near-total isolation, rarely leaving the safety and comfort of their homes, thanks to remotely-controlled robotic bodies that serve as "surrogates," designed as better-looking versions of their human operators. Because people are safe all the time, and damage done to a surrogate is not felt by its owner, it is a peaceful world free from fear, pain, and crime. Agent Greer is an FBI agent who, through the use of his own surrogate, investigates the first murder in years: Jarod, the college student son of the man who invented the surrogates and uses multiple surrogates himself. The case grows more complicated, however, when several humans are murdered because their surrogates are destroyed. The withdrawn detective discovers that in order to actually catch the killer he will have to physically venture outside the safety of his home for the first time in many years, and enlists the aid of another agent in tracking his target down.
Greer begins investigating the murder and is lead to the Dreads, a group of humans led by a mysterious man known only as The Prophet who are against the use of surrogates. One of the Dreads, Miles, used a weapon to kill Jarod as well as five cops tracking him with the weapon. Despite his surrogate being badly damaged by the weapon, Greer survives by unplugging as it is fired and later plugs back in afterwards and chases Miles down before his surrogate is destroyed by the Dreads. Greer is badly hurt by the weapon despite disconnecting. He is found by his wife Maggie (who acts entirely through her surrogate and has not been face-to-face with her husband in her real body ever since their son died in a car accident). Greer is taken to the hospital and survives, although he is suspended and is not allowed to use a surrogate while his actions are under investigation.
At the Dread Reservation, Miles is approached by The Prophet who demands information then apparently kills him. When Greer goes into the Reservation, he stumbles upon Miles' funeral and then approaches The Prophet asking about the weapon Miles used. As Greer leaves the Reservation, it is revealed that The Prophet has the weapon. Greer meets with Doctor Canter, again using one of his surrogates, who suggests the weapon was manufactured by the military. Greer meets with a member of the military and learns that the weapon sends a virus into the surrogates that shuts them down, but it also disables the failsafes and kills the operator.
A mysterious surrogate goes to the home of Peters, Greer's partner, and kills her, transferring control of her surrogate to an unknown party who uses it to go through the financial records of the FBI. Peters learns that Stone, his boss, is apparently behind the death of Jarod, having been delegated by the company that creates the surrogates to kill Doctor Canter which he in turn assigned to Miles. Jarod was using one of his father's surrogates and as such was mistaken for him. At the Dread compound, The Prophet orders delivery of the weapon to Peters just before the military attacks. The Prophet and his men are killed and The Prophet is revealed to be a surrogate of Doctor Canter. Peters tricks Greer into getting information from Stone's hardrive on the weapon which shows Stone knew that The Prophet was Canter and gets the weapon activation code. Peters then flees from Greer and takes off with the information and the weapon. Greer chases her, but she gets away and goes to FBI headquarters where she takes a system administrator, who does not use a surrogate, hostage and hooks the weapon up the surrogate network to kill all the surrogate operators.
Greer calls the sysop who reveals that Peters has taken him hostage before he is knocked out. Greer heads to Canter's home and after taking out one of his guards, heads off to find the real Canter. At the FBI building, Peters forces Stone to come talk to her and it is revealed Canter is now controlling the Peters surrogate. Stone confirms he did try to have Canter assassinated and Canter kills him with the weapon and returns to uploading the weapon's virus to all the surrogates. Greer makes his way through Canter's mansion and finds Canter's many surrogates which includes the one that killed the real Peters. He then finds Canter (who disconnects from Peters) who then reveals he wants to destroy the surrogates so that real humans can return to their prior lifestyle. Canter has already started the process through Peters and then kills himself. Greer takes control of Peters and with the assistance of the sysop, insulates the surrogate operators so they will survive even if the surrogates go down. He is then given the choice of whether or not to save the surrogates. The FBI storm the room as Greer decides not to cancel the transmission before the Peters surrogate is killed. The virus from the weapon uploads and destroys every surrogate worldwide, leaving their operators alive, but having to go back to using their real bodies again. Greer goes home and connects with his wife in her real body for the first time in years. Media broadcasts reveal the surrogates are down worldwide and no one knows if they will ever be able to be recreated again.
- Bruce Willis as Agent Harvey Greer, a FBI agent who investigates the murder of others' surrogates
- Radha Mitchell as Agent Peters, Agent Greer's partner
- Rosamund Pike as Maggie Greer, Agent Greer's wife
- Ving Rhames as The Prophet, a cult figure who disdains surrogates and plans an uprising.
- Boris Kodjoe as Andrew Stone
- Jack Noseworthy as Strickland
- James Cromwell as Dr. Lionel Canter, the inventor of the surrogates
- James Francis Ginty as Dr Lionel Canter younger Surrogate