This was the first episode where the animation was produced by Film Roman. Up until this point, Film Roman had mostly worked on Garfield and Friends (1988) and Bobby's World (1990) episodes, and were not used to the speed with which this series was produced. However, they quickly adjusted. Film Roman went on to do the animation for the rest of the series, including The Simpsons Movie (2007), up to Season 28's Havana Wild Weekend (2016). Previously, the animation was produced by Klasky Csupo, and as of 2016 is produced at 20th Television Animation.
The abrupt cutting off of God's voice before he reveals the meaning of life was intended to be cut off by a voiceover promotion for whatever Fox program aired afterwards. However, Fox did not pick up on this and so God's voice was instead cut off by the show's credits.
In the scene in which Jimi Hendrix and Benjamin Franklin play a game of air hockey in Heaven, Hendrix was supposed to have a speaking line of his own to respond to Franklin's line. It was cut late during production because the voice actor for Hendrix did not sound enough like Hendrix. Franklin's line was kept because "nobody knows what he sounds like", whereas Hendrix had a distinct voice.
God and Jesus are the only characters in the series to have five fingers on each hand.
At the end of the episode Homer asks God what the meaning of life is to which he says he'll find out in 6 months when he dies. Six months after the debut of this in So It's Come to This: A Simpsons Clip Show (1993) Bart plays a prank on Homer which lands him in the hospital nearly killing him.