The film is the adaption of the novel Casino which circles around the lives of mob associates Frank Rosenthal (renamed Sam Rothstein for the movie), Tony Spilotro (renamed Nicholas "Nicky" Santoro), Joseph Aiuppa (Remo Gaggi) and Frank Cullotta (Frank Marino). Rothstein and Santoro narrate the film.
Rothstein is entrusted by the leaders of the Chicago outfit, led by Gaggi, to manage a Las Vegas casino they financed and send them skimmed profits. Rothstein's friend Santoro shows up later and starts working for himself. While Rothstein appears to be a kind-hearted gentleman, Santoro is the polar opposite: an amoral psychopath who will not hesitate to kill anyone he sees a threat. In one scene, after Santoro is asked by Gaggi to protect Rothstein, Santoro stabs a man in the neck with a pen solely for insulting Roth, then mocks the man's whimpers. His cruelty also comes to the surface at another point when he takes his anger out on the Casino Manager, Billy Sherbert (Don Rickles) and hits him in the face with a telephone, calling him a Jew Fuck.
But Rothstein and Santoro's relationship meets its biggest test when a woman named Ginger McKenna (based on Geraldine McGee) comes into Rothstein's life. After dating for a few years, they get married and have a daughter. All seems well, until Ginger is caught sneaking around with her old boyfriend, Lester Diamond (based on Lenny Marmor). Rothstein and Santoro have their men beat Diamond up, but it doesn't stop him. Ginger and Diamond eventually kidnap the daughter, Amy, and flee for some unknown location, until Rothstein phones them up and convinces Ginger to bring Amy back home.
Though not satisfied, Rothstein accepts Ginger back inside the house, but that night, Rothstien catches Ginger speaking on the phone, asking someone to assassinate Rothstein. Furious, Rothstein hangs the phone up, makes Ginger pack up her stuff and forces her out of the house. She comes back later on, but Rothstein has an even harder time accepting her back.
Now wanting to leave Rothstein with her money, Ginger seduces the one man who will help her: Santoro. They have an affair. But it all reaches the breaking point when Rothstein and Santoro have a falling out when Santoro's reckless criminal activities bring unwanted attention from the police. Rothstein tries to get Santoro to keep a lower profile, but he will not listen.
One night, Rothstein goes home and finds Amy tied to the bedposts - by Ginger. Santoro calls Rothstein, and tells him that Ginger is at the casino with him. Furious, Rothstein rushes back to the casino, pushes Santoro aside and confronts Ginger, warning her that should she ever do that to Amy again, he will murder her. Rothstein forces her out, but she sneaks back inside when Rothstein goes.
Ginger blames Santoro for the mess, while Santoro tells her it was her own fault. Angered, Ginger attacks Santoro, who, showing his brutal nature, throws her out of the casino.
The next day, Ginger goes to Rothstein's home, and demands that he hand over her share of the money and her jewelry. Rothstein hands it over, and Ginger collects it from the bank, but she is caught speeding, and taken to the police station.
Prior to his fatal beating, Nicky is forced to watch his brother, Dominick, being beaten first.
Then the empire crumbles. The big bosses, ruled by Gaggi, decide to get rid of anybody who could incriminate them. They kill a lawyer named Andy Stone, three casino executives, the money courier John Nance (Nance's son was in trouble with the FBI for drugs, and Nance was killed so that he wouldn't be able to go to court and give the bosses up to save his son), and ultimately, Nicky Santoro and his brother Dominick, who are beaten to a pulp and buried alive in a cornfield in Indiana as an object lesson: Frank Marino participates in the beating of the Santoro brothers, claiming that he has had enough of their dirty work. It's hinted that Ginger is killed by the people that she ran with after leaving Rothstein; she dies of a drug overdose.
Rothstein himself is nearly killed by a car bomb. Knowing that it was too amateurish to have been ordered by the bosses, Rothstein goes back to working as a sports handicapper for them.
Although it is not shown in the film, the Santoro brothers are eventually dug up and given a proper burial, and Remo Gaggi is eventually arrested and sentenced to life in prison, where he dies at age 89.
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