This thread will focus on main characters or series regulars being absent from at least one episode of a particular series for zero valid reason whatsoever (meaning not due to behind-the-scenes issues like contract negotiations, or walking-out on set and intentionally missing tapings for episodes).

Also, who is uneasy about main-characters'/castmembers' absences? And have you ever refused to watch an episode of a particular series just because your favorite main character is absent from said episode?

Richie Iannucci - King of Queens
Sarah Spooner - King of Queens
Stanley the dog - King of Queens
Judy Winslow - Family Matters
Regina ? - Mom

They should have at least brought Chuck Cunningham back for Richie's wedding. The whole "We have two wonderful kids" thing Mr. Cunningham says near the end sounds so sinister.

In Season 4 of Angel, Cordelia is weirdly written out of many of the episodes. Never made sense to me, as she was the leading lady, and there was no contract dispute. It's like the writers just forgot how to write her character... or to write it at all.

My beloved Facts of Life Lost Girls. No contract dispute... just network tinkering. Network exec Warren Littlefield erroneously claimed there were "ten, twelve girls" on the show, and because he couldn't count to seven, half the cast got the axe. Nancy and Sue Ann at the very least should have been at their own graduation ceremony, with Blair and Jo. There was no excuse for that.

It was so weird how the cast on the Ellen sitcom kept changing. By the end, they had a completely different cast than what they started with... aside from Ellen, of course. In retrospect, considering how Ellen is alleged to have treated people on her talk show, maybe that's no surprise.