“Stewie Kills Lois/Lois Kills Stewie,” Season 6, Episodes 4 & 5, Original Airdates: 11/4/07 & 11/11/07

Callaghan: After 100 episodes of Stewie talking a big game about killing Lois, he actually pulls it off. It was the years-long payoff for one of the most bedrock relationships in the series.
MacFarlane: At the end of this two-episode arc, it turned out the whole thing was a dream, which really satisfied the fans.