- The end of "The Bachelor Party" where Drew watches the sex tape he made with his fiancée and the audience learns it's an attempted sex tape where his fiancée realizes she's regained her old weight and breaks up with Drew, saying it's his fault she became fat because she "can't be around someone who loves to eat". At the end of the episode he rewinds it and watches it over and over. Made worse since her parents used this same phrase to describe Drew in an earlier episode but it was played for laughs.
- Really, the fact that Drew's love life is such a trainwreck in the first place, given that he is a genuinely good, kind person who honestly attempts to put others first. Sometimes at the cost of his own happiness.
- When Mr. Wick is caught with cocaine, he plays it off until Drew insists he's got to go to rehab. He sits down in his chair and with a weak broken voice mutters "I'm suddenly very tired." Even more so when you remember Craig Ferguson's real-life struggle with drug addiction and alcoholism.
- The end of the second episode of season 8. After Kate's wedding to another man, Drew, Oswald, and Lewis are in Drew's living room watching TV. Drew has a thousand-yard stare on his face due to the fact that he just said goodbye to the love of his life and lifelong best friend, Kate.
Tear Jerker / The Drew Carey Show