- Creator Backlash: Angus Jones (who played Jake) left the show at the end of season 10 after he converted to Seventh-Day Adventism. He now treats it as an Old Shame, claiming that it is immoral and that he had been a "paid hypocrite" by starring on it.
- Creator Breakdown: The circumstances surrounding Charlie Sheen's exit are an explosive example.
- The Danza:
- Charlie Sheen as Charlie Harper.
- Paula Marshall as Paula, Alans Transgender girlfriend from ep. 9-10 of season 11.
- Dyeing for Your Art: Jon Cryer's hair began to thin dramatically and, while he was open about it, the hair and makeup department used a powdered hair loss concealer to make it seem he still had a full head of hair. After the series ended, he shaved his head and grew a beard
- Fake American: Rose, played by New Zealander Melanie Lynskey.
- Fake Shemp: No, that's not Charlie Sheen you're seeing from behind as his old character in the Grand Finale.
- Follow the Leader: Starting with Season 10, the show started to incorporate quite a bit of the geeky humor that made The Big Bang Theory so popular. Justified in that the jokes are more fitting to Walden's character and background than the Charlie-esque storylines the show was still trying to use in Season 9... and the fact that Chuck Lorre produces both shows.
- McLeaned: Charlie was killed off by being pushed in front of a train after he was caught cheating on his fiance, Rose. And just to add insult to injury, the funeral is full of one night stands and angry exes. And after he is cremated, Walden's first appearance has Alan spilling Charlie's ashes all over the ground. Then Alan vacuums Charlie's remains with a dustbuster.
- Money, Dear Boy: A variation; the main reason why Chuck Lorre pushed the network to commission a pilot was because co-creator Lee Aronsohn would cease to be eligible for WGA health coverage if one of his scripts wasn't put into production very soon. Fortunately for all concerned, it turned out that the network quite liked the pilot...
- The Other Darrin: Delores Pasternak was originally played by Missi Pyle. When she returned two years later, she was played by Alicia Witt. In brief appearances in later seasons, Missi Pyle came back.
- Playing Against Type: Ryan Stiles. Lewis was a Jerkass and a borderline sociopath while Herb is one of the nicest people on the show.
- Real-Life Relative: Charlie Sheen's brother Emilio Estevez made a guest appearance.
- What Could Have Been: The original plan for the ending of the series, according to Chuck Lorre's vanity card: "I know a lot of you might be disappointed that you didn't get to see Charlie Sheen in tonight's finale. For the record, he was offered a role. Our idea was to have him walk up to the front door in the last scene, ring the doorbell, then turn, look directly into the camera and go off on a maniacal rant about the dangers of drug abuse. He would then explain that these dangers only applied to average people. That he was far from average. He was a ninja warrior from Mars. He was invincible. And then we would drop a piano on him. We thought it was funny. He didn't. Instead, he wanted us to write a heart-warming scene that would set up his return to prime time TV in a new sitcom called The Harpers starring him and Jon Cryer. We thought that was funny too."
- Write What You Know: Chuck Lorre has experience as a jingle writer; he wrote the theme song for Teenage Mutant Ninja Turtles. Overlaps with Actor Allusion (Creator Allusion?) when Charlie plays said theme song on the piano for Jake in an early episode, only for Jake to be utterly clueless about where it's from.
- Write Who You Know: Charlie Harper's characterization is basically that of his actor, Charlie Sheen. It's even referred to as such by Trifecta.
- You Look Familiar:
- The actress who plays Chelsea, one of Charlie's few meaningful relationships for a long time (some would say too long) had already appeared in other roles in previous episodes, including the Pilot.
- April Bowlby, who later played Kandi, made an earlier appearance playing a woman in Charlie's shower, called "Bubbles." It is possible Bubbles was Kandi, as Kandi shows up two episodes later and acts just like her (April Bowlby is credited as "Kimber" in that episode, even though she's never addressed as such in the entire episode).
- Jenna Elfman appeared in a two-part episode in the first season as a woman named Frankie. She later appeared as Dharma in the Season 9 opener.
- Judy Greer, who plays Walden's wife appeared in the fourth season as Herb's sister, Myra.
Trivia / Two and a Half Men