Sam Elliot's character is based on real "Marlboro Man" model Wayne McLaren, who contracted lung cancer, testified for anti-smoking legislation, and had the Phillip Morris Company try to deny he was in the ads. Two other models - David McLean and Dick Hammer - also died of lung cancer. A fourth, Eric Lawson, died of respiratory failure due to chronic obstructive pulmonary disease, or COPD, at the age of 72 in 2014.
William H. Macy came up with the line "The great state of Vermont will not apologize for its cheese". His original line was "Why you son of a..."
When Heather is watching Nick speak to the press on the TV (after the Washington Probe article), the name Theresa Greene is seen on a placard on one of the cubicles in the office. Theresa Greene was the art department coordinator for the movie.
When Nick Naylor is sitting with his son Joey Naylor waiting to meet Jeff Megall, they are watching BBC's The Blue Planet (2001).
17 minutes into the film you see an ad "More doctors smoke Alpacas than any other cigarette." This is a spoof on Camels cigarettes, which used that slogan on paper and on old time radio advertisements.