Kat Foster and Eddie Kaye Thomas, who played neighbors Steph and Jeff Woodcock, left the show after season 2 to pursue other projects, though episodes featuring their characters continued airing into seasons 3 and 4 due to production delays.

J.B. Smoove joined the cast late in season two as Eddie's friend Kenny, was promoted to main cast for season three, but was then dropped back from the main cast for the episodes produced in season four.

The character of Allison Stark was played by five different actresses over the course of the series (Krysten Ritter, Laura Clery, Lindsey Broad, and Kate Micucci), and this recasting eventually became a running gag referenced in later episodes.

Production of season two was halted in late 2007 due to the Writers Guild of America strike, resulting in only 19 episodes being produced instead of the originally planned amount.

Season three consisted of 22 episodes, but four of them had actually been produced during season two's production batch; several unaired season three episodes were later burned off during season four's run, including four that aired back-to-back on Christmas Day.

Despite persistently low ratings and only airing part of season three, 'Til Death was surprisingly renewed for a fourth season in January 2009, a decision attributed to Sony Pictures Television offering Fox a significant licensing discount so the show could reach the episode count needed for syndication.

The show's ratings notably improved in March 2007 when it was moved to the time slot directly following American Idol's results show.