Nick Naylor (AARON ECKHART) is the Vice-President of Tobacco Studies, the main lobbying firm for the tobacco industry. Although divorced from his ex-wife Jill (KIM DICKENS) and barely around for his son, Joey (CAMERON BRIGHT), Nick's the best spin doctor in the business who firmly believes in the mantra that that if you argue correctly, you're never wrong.
When he's not commiserating with the other members of the M.O.D. (Merchants of Death) Squad -- alcohol lobbyist Polly Bailey (MARIA BELLO) and gun industry spokesman Bobby Jay Bliss (DAVID KOECHNER) -- Nick directly works for BR (J.K. SIMMONS) who gets his marching orders from the Captain (ROBERT DUVALL), the revered, big boss of the tobacco industry.
Nick's latest foe is democrat U.S. Senator Ortolan Finistirre (WILLIAM H. MACY) who wants to put more graphic warning labels on cigarette packaging. But Nick's more interested in trying to convince Hollywood super-agent Jeff Megall (ROB LOWE) to do more tobacco-related product placement in his movies, while also delivering a bribe to Lorne Lutch (SAM ELLIOTT), the original Marlboro man who's dying from a life of smoking. And then there's Washington Probe reporter Heather Holloway (KATIE HOLMES) who's set her sights on Nick, blinding him to her real agenda.
While dealing with all of that and getting to know Joey who's along for the ride and observes his dad at work, Nick does what he can to convince everyone that while cigarettes might be bad, it's up to the individual to decide if they're right for themselves.