The comic covers a wide range of subjects, such as love, sex, work, and death, and explores themes of angst, social alienation, self-loathing, and fear of inevitable doom.

Life in Hell caught the attention of producer James L. Brooks, who resultantly hired Groening to create animated shorts for The Tracey Ullman Show.

[1] It was inspired by his move to the city that year; in an interview with Playboy, Groening commented on his arrival: "I got [to Los Angeles] on a Friday night in August; it was about a hundred and two degrees; my car broke down in the fast lane of the Hollywood Freeway while I was listening to a drunken DJ who was giving his last program on a local rock station and bitterly denouncing the station's management.

"[2] Groening photocopied and distributed the magazines to friends, and also sold them for two dollars a copy[2] at the punk corner of the record store in which he worked, Licorice Pizza on Sunset Boulevard.

The magazine covers were humorous as well: the first issue saw Binky, a rabbit-humanoid character, standing in a cloud of smog and declaring, "What you see is what you breathe."

[3] Then-publisher of the Reader Jane Levine said Groening arrived at editor-in-chief James Vowell's office one day, showing him his "silly cartoons with the rabbit with one ear."

[6][7] In 1985, Brooks contacted Groening with the proposition of developing a series of short animated skits, called "bumpers", for The Tracey Ullman Show.

Groening opted to not use the Life in Hell characters for the shorts, concerned that if the cartoons were not successful it would adversely affect the strip.

[8] As television began to place more demands on his time, however, Groening came to almost exclusively feature single-panel strips or 16-panel grids in which Akbar and Jeff exchange terse jabs.

Other strips had one large panel, This is based on the way Lynda Barry made comics when they were in college, and the way it was published originally in the Reader.

In addition to the books, the comic also spawned T-shirts, sweatshirts, greeting cards, posters,[5] coffee mugs, and a short-lived newsletter called the "Life in Hell Times".

[21] In the late 1980s, Groening drew several print advertisements for Apple Computer in the form of Life in Hell comic strips.

At the 2005 Comic-Con in San Diego, a series of deluxe Life in Hell vinyl figurines manufactured by CritterBox Toys was announced.