Most of the series takes place within the confines of the fictitious Colorado Casino in Las Vegas. There, a group of professional poker players has banded together to take down legendary gambler Don "The Matador" Everest (Michael Madsen) in a cash game. Each player has his own reason for wanting to hurt Everest, including a cop, Lee Nickel (Chris Bauer), who wants to see him in jail for killing Nickel's brother.

Everest, as it turns out, is a sophisticated poker cheat. His preferred cheating method is collusion with hired partners (Everest calls them his "horses") at the same table, who signal their hole cards to Everest by flashing subtle hand signs. Toward the end of the series, during the WCoP tournament, Everest's horses also help him advance in the tournament by accumulating chips during their own play, then "dumping" them to Everest by intentionally losing to him and passing them during breaks. Everest runs his cheating racket in much the same manner as a Mafia boss, treating his loyal partners lavishly but also coming down brutally on those who violate his trust (up to and including murder, thus giving his "Matador" nickname a whole new literal meaning), and bribing Colorado Casino officials and even local law enforcement to turn a blind eye toward his illegal activities.

One member of the group arrayed against Everest, Eddie Towne (Eddie Cibrian), manages to gain the Matador's trust and is offered a role as one of his horses. This enables Towne to learn firsthand how Everest operates, and eventually to set up a high-stakes game involving himself, his partners and Everest, in which he and his partners plan to use the Matador's own signaling system against him. Unfortunately for them, they learn the hard way that Everest was onto them from the beginning. Towne is brutally cast out of Everest's stable, and his partners are forced to abandon their stake money to Everest (as the price for not having charges pressed against them for their own attempt at cheating).

No longer able to break Everest at the poker table, Towne's group decides to take a different approach: Join forces with Nickel to try and turn Everest's associates against him. Nickel has also gained another ally: erstwhile Colorado Casino executive Bart "Lowball" Rogers, recently ousted for crossing Everest one too many times. Lowball stakes Towne and his partners the $10,000 buy-in for the WCoP tournament, so that they can keep Everest preoccupied while he and Nickel put the heat on his henchmen.

Meanwhile one of Towne's partners, Clark Marcellin (Todd Williams), brings Everest's cheating racket and attendant murders to the attention of an undercover FBI agent. In between WCoP playing sessions, Towne and his partners help the agent build a federal case against Everest. Ultimately Everest and Towne become the last two players left in the WCoP tournament. Towne wins the heads-up battle, only to learn later that Everest had deliberately thrown the hand - and had his daughter bet enough money on Towne to more than cover the prize difference between first and second place. Everest is then arrested by the FBI, but in the closing moments of the final episode a key witness against Everest is found hanged in a shower stall, as an apparent suicide.

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