In 1963 Oregon, Randle Patrick "Mac" McMurphy (Jack Nicholson), a recidivist anti-authoritarian criminal serving a short sentence on a prison farm for the statutory rape of a 15-year-old girl, is transferred to a mental institution for evaluation. Although he does not show any overt signs of mental illness, he hopes to avoid hard labor and serve the rest of his sentence in a more relaxed hospital environment.
Child psychologist Catherine Deane (Jennifer Lopez) is an expert in an experimental treatment for coma patients: a virtual reality device that allows her to enter into the minds of her patients and attempt to coax them into consciousness. When serial killer Carl Rudolph Stargher (Vincent D'Onofrio) falls into a coma before the FBI can locate his final victim, Agent Peter Novak (Vince Vaughn) persuades Deane to enter Stargher's mind and discover the victim's location. Stargher's victim is imprisoned in a cell in the form of a glass enclosure that is slowly filling with water by means of an automatic timer.
Adam, a young photographer, awakens in a filthy bathtub. He gets out and finds himself chained to by one foot to a pipe in a large dilapidated bathroom. Lawrence Gordon, an oncologist, is chained by one foot to a pipe across the room and between them lies a corpse, holding a revolver and a microcassette recorder. Adam manages to retrieve the recorder and they learn from tapes in their pockets what they must do: Adam must escape the bathroom, and Lawrence must kill Adam before six o'clock, or his wife and daughter will die and he will be left to die as well. Using a clue from the tape, Adam finds a bag in the toilet tank containing two hacksaws, though neither is able to cut through their chains. Adam's saw breaks and he throws it at a mirror in frustration. Lawrence realizes the saws are meant to be used on their feet and identifies their captor as the Jigsaw Killer, whom Lawrence knows of because he was once a suspect.
After spending eight years in prison for rape, Max Cady (Robert Mitchum) is released. He promptly tracks down Sam Bowden (Gregory Peck), a Georgia lawyer whom he holds personally responsible for his conviction because Sam interrupted his attack and testified against him. Cady begins to stalk and subtly threaten Bowden's family. He kills the Bowden family dog, though Sam cannot prove Cady did it. A friend of Bowden's, police chief Mark Dutton (Martin Balsam), attempts to intervene on Bowden's behalf; but he cannot prove Cady guilty of any crime.
Private investigator Tom Welles (Nicolas Cage) is contacted by Daniel Longdale (Anthony Heald), attorney for wealthy widow Mrs. Christian (Myra Carter), whose husband has recently died. While clearing out her late husband's safe, she and Longdale found an 8mm film which appears to depict a real murder of a girl, but Mrs. Christian wants to know for certain.
Growing up, Evan Treborn, and his friends, siblings Kayleigh and Tommy Miller, and Lenny, suffered many severe psychological traumas that frequently caused him to black out. These traumas include being coerced to take part in child pornography by Kayleigh and Tommy's father, George Miller (Eric Stoltz), being nearly strangled to death by his institutionalized father, Jason Treborn (Callum Keith Rennie), who is then killed in front of him by guards; accidentally killing a mother and her infant daughter while playing with dynamite with his friends; and seeing his dog being burned alive by Tommy.
In the 1960s, a young woman nicknamed Babydoll (Emily Browning) is institutionalized by her abusive widowed stepfather (Gerard Plunkett) at the Lennox House for the Mentally Insane after she is blamed for the death of her younger sister. The stepfather bribes Blue Jones (Oscar Isaac), an asylum orderly, into forging the signature of the asylum's psychiatrist, Dr. Vera Gorski (Carla Gugino), to have Babydoll lobotomized so she cannot inform the authorities of the true circumstances leading to her sister's death. During her admission to the institution, Babydoll takes note of four items that she would need to attempt an escape.
College students Paxton (Jay Hernandez) and Josh (Derek Richardson) are traveling across Europe with their Icelandic friend Óli (Eyþór Guðjónsson). In Amsterdam, the three meet a man named Alexei (Lubomir Bukovy), who convinces them to visit a hostel in Slovakia filled with beautiful women. The three board a train to Slovakia, where they encounter a strange Dutch businessman (Jan Vlasák). When they arrive at the hostel, they are greeted by Natalya (Barbara Nedeljáková) and Svetlana (Jana Kaderabkova), who invite them to the spa, and later to the disco. That night, Paxton and Josh sleep with Natalya and Svetlana, while Óli sleeps with the desk girl, Vala (Jana Havlickova). The next morning, they are surprised to see that Óli hasn't returned, and they are unable to contact him. They are later approached by a Japanese girl named Kana (Jennifer Lim), who shows them a photo of Óli and her friend Yuki (Keiko Seiko), who has strangely disappeared as well.
A career bank robber, Jack Foley (George Clooney), and a U.S. Marshal, Karen Sisco (Jennifer Lopez), are forced to share a car trunk during Foley's escape from a Florida prison. After he completes his getaway, Foley is chased by Sisco while he and his friends—right-hand man Buddy (Ving Rhames) and unreliable associate Glenn (Steve Zahn)—work their way north to Bloomfield Hills, a wealthy northern suburb of Detroit. There they plan to pay a visit to shady businessman Ripley (Albert Brooks), who foolishly bragged to them in prison years before about a cache of uncut diamonds hidden in his home.
In 1888, Mary Kelly (Heather Graham) and her small group of London prostitutes trudge through unrelenting daily misery. When their friend Ann Crook (Joanna Page) is kidnapped, they are drawn into a conspiracy with links higher up than they could possibly imagine. The kidnapping is soon followed by the gruesome murder of another woman, Martha Tabram (Samantha Spiro); and it becomes apparent that they are being hunted down, one by one as various prostitutes are murdered and mutilated post-mortem.
Frank Moses (Bruce Willis), a former black-ops CIA agent, is retired and living a quiet life in a Cleveland, Ohio, suburb. However, Frank is lonely and often chats on the phone with Sarah Ross (Mary-Louise Parker), a Customer Service Agent for the General Services Administration Pension Office in Kansas City, Missouri. He creates opportunities to talk to her by tearing up his pension checks and calling her to say they had never arrived.
Predatory lenders Simone and Eddie awaken on either side of a room split by a cage containing a scale, wearing head harnesses with screws poised to pierce their temples. They learn via videotape that the one who sets more flesh weight on their tray will survive. Eddie cuts fat from his torso, but Simone chops off her arm, which tilts the scale in her favor; the timer expires, and Eddie is killed by the screws. While he reviews the game's footage, Detective Lt. Mark Hoffman is called to the scene by FBI Agent Dan Erickson, who found Agent Peter Strahm's fingerprints around the room. Also present is Agent Lindsey Perez, whose survival was covered up by Erickson for her protection. They learn from Dr. Adam Heffner, who performed all of the autopsies for the Jigsaw case, that the knife used to cut the jigsaw piece from Eddie's flesh was only used on Seth Baxter before then. The agents intend to find the Baxter videotape to prove Strahm's involvement.
Rafi (Uma Thurman) is a recently divorced, 37-year-old career woman from Manhattan who becomes romantically involved with David (Bryan Greenberg), a talented 23-year-old Jewish painter from the Upper West Side. Rafi shares all her secrets with her therapist Lisa (Meryl Streep) who, unbeknownst to Rafi, is David's mother. Lisa, supportive of Rafi's relationship with a younger man, discovers the connection and finds herself not only faced with the ethical and moral dilemma of counseling David's girlfriend, but also the reality that she feels differently about the relationship now that she knows her son is involved. Lisa consults her own therapist, and they decide that it is in the best interest of her patient Rafi for Lisa to continue treatment, as long as the relationship remains the "fling" it appears to be.
Two friends and convicts, Joe (Bruce Willis) and Terry (Billy Bob Thornton), break out of Oregon State Penitentiary in a concrete mixing truck and start a bank robbing spree, hoping to fund a dream they share. They become known as the "Sleepover Bandits" because of their modus operandi: they kidnap the manager of a target bank the night before a planned robbery, then spend the night with the manager's family; early the next morning, they accompany the manager to the bank to get their money. Using dim-witted would-be stunt man Harvey Pollard (Troy Garity) as their getaway driver and lookout, the three successfully pull off a series of robberies that gets them recognition on the FBI's Ten Most Wanted list.