- Jeffrey Ross's last routine in his one episode is actually pretty sad, where he shares a poem he wrote called "Either She Screens Her Calls Or She Hasn't Been Home Since 1985":Jeffrey: "Hello, pick up the phone, I know you're home... I'll just try back later."
- Dom Irrera was one of the funniest guests, but he had a surprisingly sad bit in "Reunion":Dom: You know what depression is, doc? I wake up for breakfast, and then I have a little bit of Cap'n Crunch, I laugh, I play in the bowl, I look for things in the milk, and then I fall asleep. I force myself to sleep. That's depression, doc.
Dom: It's very hard... (voice breaking) I'm sorry, I promised myself I wasn't gonna cry today. I am so sorry.
- There's also his brief breakdown in the first episode after discussing his bad home life, which is surprisingly not played for laughs like other instances in the series.
Dr. Katz: Just let it out.
- Bob Balaban in "Expert Witness". His extreme amount of misfortune in a short window of time was probably meant to be Dark Comedy, but it just comes across as depressing. To recap: His wife is leaving him, a relative committed suicide, he lost a lot of money, and he has a brain tumor. Jeesh.
Tearjerker / Dr. Katz, Professional Therapist