- We follow the journey of James Cole, a time traveller from a post-apocalyptic future, who heads to the present to stop a plague that will eventually decimate the human race.
- 27 years after a virus wipes out most of humanity, scientists send a man (James Cole) back to 2015 to stop the plague from ever happening. Cole's only lead is a virologist (Dr. Cassandra Railly), who knows the dangerous source of the outbreak.
- James Cole travels back in time from 2043 to 2013 in the hopes of stopping the outbreak of a deadly disease that has its origins in 2017. He kidnaps virologist Dr. Cassandra Railly but quickly realizes they have sent him too far back in time as she has yet to meet a key player in the timeline, Leland Frost. She thinks he's insane but he quickly demonstrates how the timeline can be changed and then promptly vanishes before her very eyes. They meet again in 2015 where he tells her that in 2017, the plague killed most of the world's population, 7 billion people. Cole's mission is find away to stop the plague from happening in the first place - and that she mentioned his name in a radio message before she died. Leland Frost has been found but his name is actually Leland Goines, CEO of the Markridge Group which engages in various Defense Department activities. When they finally do meet up, Goines recalls meeting meeting Cole in 1987 - but Cole is certain he hasn't met him yet. It quickly becomes clear that Goines isn't the cause of the plague.—garykmcd
- In 2043, James Cole and his partner search the ruins of an earth desolated by a viral plague, years earlier. They discover a watch on the wrist of a skeleton in one of the buildings. "See you soon." Cole says.
In 2013, virologist Cassandra Railly gives a talk about the dangers of a coming viral epidemic, or even pandemic. Afterwards, she walks to her car, while talking on the phone to her boyfriend Aaron Marker. When she gets in the car, Cole is in the back seat. He grabs her, and she yells for Aaron to call the police. Cole threatens her with a knife if she does not comply and orders her to drive. As they drive, he questions her about a man named Leland Frost, who she insists that she does not know. Cole takes her to a building where he explains that he is from the future and that he needs to find Frost to stop an oncoming viral apocalypse. He shows Railly the watch he found in the future, which is the same as the watch she is wearing. As she watches, he sratches a line into her watch, causing one to appear on the watch from the future. As the police approach, Cole continues to try and explain himself. He is shot by the police but explains to Railly that if she believes him she should meet him at a hotel in Philadelphia, two years in the future. He then disappears before Railly's eyes.
In 2015, Railly sits in the hotel bar, vainly waiting for Cole to arrive. She has been there a week and finally decides to check out when Cole stumbles into the hotel, still wounded. She takes him to her room and begins to treat his wound, as he passes out. Cole has a flashback to when he was recruited in the future by a scientist named Jones to go back in time, or splinter, and find Frost. When he awakens Railly notes that he heals unusually fast. She also tells him that she has since lost her job due to people thinking her story about him was crazy. Cole tells her that in the future she had worked for the CDC, trying to contain the outbreak. The scientists had discovered a garbled voice recording from her which referenced Leland Frost as being involved in the origin of the outbreak. Cole asks if she has found Frost in the intervening two years and she replies that she hasn't.
Cassandra takes Cole to see Jeremy, a retired NSA operative who was a friend of her father's. He has been looking into Leland Frost for her. He explains that they had not been able to find an appropriate Leland Frost because that was not the name they were searching for. Instead, he gives them a file about a Dr Leland Goines, the CEO of Markbridge laboratories, a bioengineering firm. Goines has the security codename "Frost".
Markbridge will be having a party the next night in Washington, with Goines in attendance, as well as Senator Royce, Aaron Marker's employer. Cole plans to go to the party and murder Goines, which will change history and cause Cole to wink out of existence. Cassandra protests that whatever caused the plague might already be in motion and that killing Goines may not stop it.
They bluff their way into the party, where Cassandra begins talking to Goines. Cole disarms a security guard, taking his gun. As he approaches Goines, Cassandra shouts for him to stop and he is subdued by security guards. Cassandra and Cole are arrested, with Aaron concerned that she is suffering from Stockholm syndrome. The police drive them to a deserted area and then hand them over to Markridge security personnel.
Goines arrives to speak to Cole. He says that he realizes that Cole is a time traveler and that he and Cole met before in 1987, and that Cole looked exactly the same. Goines says that Cole had been asking him about something called "The Army of the 12 Monkeys". Cole, however, says that he has never met Goines before. Goines asks them about why Cole has come back, but Cole refuses to tell him. Goines tells Cole that they are going to experiment on him to discover the secrets of the next generation biotechnology in Cole's body. Cole tells Goines that he's going to show him a temporal paradox. He places both copies of Cassandra's watch on a table and pushes them together. The watches begin to give off energy and time seems to slow down. Cole grabs Cassandra and runs out of the room as the others react slowly. Once they are outside of the room, there is an explosion. Cole explains that when an object from the future touches its past self the results can be dangerous.
Goines staggers out of the exploded room, dazed, and fires a gun at Cole and Cassandra before falling down. Cole walks over, takes the gun, and kills Goines. Cassandra is shocked, but she realizes that Cole has not disappeared and that the future must not have been changed. The plague will still be released. Cole goes back to his own time where he tells Jones that he killed Goines but that the plague will still be released. Cole and Jones look at an evidence wall of news clippings about the early days of the plague. In the background of one, Cole sees a piece of graffiti featuring a monkey's head surrounded by twelve smaller monkeys. He realizes that "The Army of the 12 Monkeys" must have something to do with the virus.
In 2015, one of Goines' employees visits a mental asylum where Goines' daughter Jennifer is hospitalized. He tells her that Leland left her a substantial sum of money, but she seems unresponsive. Instead she continues frantically drawing a picture of a monkey's head.
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