Rose Cooper is a San Antonio Police Department officer whose work ethic has made her too intense in her personal life. While out on a date, she scares the guy away after she defensively pulls a gun on him.
The Irish American fraternal twin brothers, Connor and Murphy MacManus, attend a Catholic Mass, where the priest mentions the fate of Kitty Genovese. Later, while celebrating St. Patrick's Day with friends, the two get into a bar brawl with three Russian mobsters who want to close the pub and take over the land it is built on. The two brothers try to reason with the mobsters, but they respond with violence, only to be quickly and embarrassingly dispatched by the brothers and other patrons of the bar. The next morning, two of the Russians seek revenge on Connor and Murphy, who kill the mobsters in an act of self-defense.
Gangster Benjamin "Bugsy" Siegel, who works for the New York mob, goes to California and instantly falls in love with Virginia Hill, a tough-talking Hollywood starlet. The two meet for the first time when Bugsy visits his friend, actor George Raft, on a film set. He buys a house in Beverly Hills from opera singer Lawrence Tibbett, planning to stay there while his wife and two daughters remain in Scarsdale.
In 1932, Prohibition-era Texas, a mysterious character named John Smith (Bruce Willis) drives into Jericho, near the Mexican border (Population: 57), in his Ford Model A Coupe. Mere moments after arriving in the city, he takes a look at a young woman named Felina (Karina Lombard), and because of that, he is surrounded by Irish mobsters led by Finn, who is working under Doyle (David Patrick Kelly), Finn promptly smashes Smiths' car and leaves it in a state of disarray, telling him that nobody can even look at the girl since she is "Doyle's property". Smith doesn't react, but instead, he checks into a small bar/hotel run by Joe Monday (William Sanderson).
Henry Hill says, "As far back as I can remember, I always wanted to be a gangster", referring to his idolizing the Lucchese crime family gangsters in his blue-collar, predominantly Italian-American neighborhood in East New York, Brooklyn. Wanting to be part of something significant, Henry quits school and goes to work for them. He is able to make a living for himself and learns the two most important lessons in life: "Never rat on your friends, and always keep your mouth shut", the advice given to him after being acquitted of criminal charges early in his career.
Christian Martin, a modest accountant in a large firm owned by Bertrand Barnier, surprises his boss by asking him for a 100% increase in his wages. Martin is on the point of proposing to a girl and doesn't want to ask for her hand in marriage while making a lowly accountant's salary.
Leone "Léon" Montana (Jean Reno) is a hitman (or "cleaner", as he refers to himself) living a solitary life in New York City's Little Italy. His work comes from a mafioso named Tony (Danny Aiello). Léon spends his idle time engaging in calisthenics, nurturing a houseplant, and watching old films.
Chev Chelios (Jason Statham) is a Chinese-based British hitman, working for a crime syndicate headed by Uglyman (Carlos Sanz). Chelios is contracted by Carlito to kill mafia boss Don Kim (Keone Young) as members of the Triads have been encroaching on Carlito's business. Carlito betrays Chelios by making it appear he assassinated Don Kim on his own, without his authorization. Ricky Verona (Jose Pablo Cantillo), an ambitious small-time criminal uses the opportunity to conspire with Carlito against Chelios; Verona will kill Chelios so the Triads do not retaliate, and then take Chelios's place as Carlito's new hired gun. While Chelios sleeps in his apartment, Verona, his brother Alex (Jay Xcala), and several henchmen break in and inject Chelios with a Chinese synthetic drug which inhibits the flow of adrenaline, slowing the heart and eventually killing the victim. Chelios wakes to find a recording left by Verona showing what he has done.
Ambitious politician Walter Chalmers (Robert Vaughn) is about to present a surprise star witness in a Senate Subcommittee hearing on organized crime. The witness, Johnny Ross (Pat Renella), a defector from the Organization in Chicago, is put under San Francisco Police Department protective custody for the weekend, 40 hours until his Monday morning appearance.
In Marseille, an undercover detective is following Alain Charnier (Fernando Rey), a wealthy French criminal who runs the largest heroin-smuggling syndicate in the world. The policeman is assassinated by Charnier's hitman, Pierre Nicoli (Marcel Bozzuffi). Charnier plans to smuggle $32 million worth of heroin into the United States by hiding it in the car of his unsuspecting friend, French television personality Henri Devereaux (Frédéric de Pasquale).
During a shootout against Chinese Triads at a San Francisco dock warehouse, FBI agents John Crawford (Jason Statham) and Tom Lone (Terry Chen) stumble across the notorious assassin Rogue (Jet Li), a former CIA assassin who now works for the Japanese Yakuza. Rogue ambushes Crawford and is about to execute him when Lone appears and shoots Rogue in the face, causing him to fall into the water. Rogue's body was never found and he is presumed dead. However, Rogue survives and retaliates against Lone, his wife and his daughter. He kills them, burns down the house, and leaves their three corpses in the ashes of their home.
Gino Felino is an NYPD detective from Brooklyn who has strong ties within his neighborhood. Gino and his partner Bobby Lupo wait to bust up a multi-million dollar drug deal. However, Gino sees a pimp violently assaulting one of his girls and intervenes. Shortly afterward, Richie Madano murders Bobby in broad daylight in front of his wife, Laurie, and his two children.
In Kansas City, 1933, near the end of Prohibition, a police lieutenant known by his last name, Speer (Eastwood), is acquainted with a former cop turned private eye named Mike Murphy (Reynolds). Speer and Murphy were once good friends, which changed after Murphy left the force.
In the fall of 2008, amidst both the American financial crisis and the presidential election campaign, a man named Johnny "Squirrel" Amato (Vincent Curatola) plans to rob an illegitimate poker game. He enlists Frankie (Scoot McNairy), a former business associate, and Russell (Ben Mendelsohn), a heroin addicted Australian expatriate who is stealing purebred dogs for money, to perform the robbery. Markie Trattman (Ray Liotta), the proprietor of a poker ring, is revealed to have previously orchestrated an inside job by paying two men to rob his own illegal poker room. He holds up under rough questioning by the hitman Dillon (Sam Shepard), though later he openly admits his involvement to various criminal figures and suffers no retaliation. Squirrel anticipates that the Mafia will automatically blame Markie for the heist.
Mafia boss Giovanni Manzoni (Robert De Niro), who has somehow offended Don Luchese (Stan Carp), a rival mafia boss, survives an attempted hit on him and his family at a barbecue. He snitches on Luchese, which sends Luchese to prison; Manzoni and his family enter an FBI witness protection program under the supervision of Agent Robert Stansfield (Tommy Lee Jones), and are relocated to a small town in Normandy.