Herman's thought processes are dramatized in a "Greek chorus"-style interpretation, with four characters representing different aspects of his personality (played by Molly Hagan, Ken Hudson Campbell, Rick Lawless and Peter Mackenzie).

During the next couple of seasons, Herman evolves into a more edgy character, more apt to develop outlandish schemes in an attempt to further his career as well as with women, and he becomes more opinionated in situations where previously, he would have conformed to rules, or been a sycophant.

Herman's "head" characters exist in a large attic room filled with toys, a lit Christmas tree, a rose-covered bower, theater seats, neon signs, arcade games, pennants and memorabilia from Ohio State University, old furniture, and numerous file cabinets (with labels like "memories", "fantasies" and "sexual past").

The regular real-life characters are as follows: Dave Madden provided voice-over narration of the show's concept during the first season's opening title sequence.

When Herman's Head was still on the air, one of its writers was a regular contributor to an online BBS forum devoted to Fox shows.

The storyline addition was viewed to have made sense, as viewers predicted that Herman and Heddy were still destined to wind up together just as Jay and Louise had.

One episode had Yeardley Smith's character, Louise, after hanging up the telephone, ask her colleague across the room, "Herman, I don't sound like that Lisa Simpson, do I?"

In the later episode "Marge vs. Singles, Seniors, Childless Couples and Teens, and Gays", when Marge Simpson asks him to sign a petition, Comic Book Guy (voiced by Azaria) explains that he only signs petitions to bring back television shows, exclaiming "America needs the wisdom of Herman's Head now more than ever."

When asked about Herman's Head on a Simpsons commentary, Azaria said people were discussing shows that actors would rather forget, stating that he "always had that.

In 2021, the "To Protect and Serve" episode of Only Murders in the Building opens with a character watching Herman's Head and describing the show's personal importance as she was growing up.