Bill O'Reilly (October 27, 2006)
Most of Letterman's contentious interviews stem from bizarre behavior from his celebrity guests. But when the host of The O'Reilly Factor visits Dave, the tension derives entirely from the two men's vast political differences. Their highlight clash was in October 2006 — and in hindsight, this exchange is a perfect time capsule of Bush-era America as the country remained bitterly divided about Iraq and confronting terrorism. Increasingly angry at O'Reilly's rhetoric and blustering righteousness, Letterman memorably snarls, "You're putting words in my mouth, just the way you put artificial facts in your head." And even at the end, he's throwing zingers, mixing self-deprecation with incisiveness: "I'll just end up by saying, I have no idea what I'm talking about. But I don't think you do, either."