Animal Man was innovative in its advocacy and for its use of themes including social consciousness (with a focus on animal rights), metaphysics, deconstruction of the superhero genre and comic book form, postmodernism, eccentric plot twists, explorations of cosmic spirituality and mysticism, the determination of apparent free will by a higher power, and manipulation of reality including quantum physics, unified field theory, time travel and metafictional technique.

The series made deep, sometimes esoteric, reference to the entire DC canon, including B'wana Beast, Mirror Master, and Arkham Asylum.

Following Morrison's run, Peter Milligan wrote a 6-issue story (#27–32) featuring several surreal villains and heroes, exploring questions about identity and quantum physics and utilizing the textual cut-up technique popularized by William S. Burroughs.

Tom Veitch and Steve Dillon then took over for 18 issues (#33–50) in which Buddy returns to his work as a movie stuntman and explores mystical totemic aspects of his powers.

Jamie Delano wrote 29 issues (#51–79) with Steve Pugh as artist, giving the series a more horror-influenced feel with a "suggested for mature readers" label on the cover.

This event ran across the Annuals of the five then-Vertigo titles – Animal Man, Swamp Thing, Black Orchid, The Books of Magic and Doom Patrol – book-ended by two Children's Crusade issues co-written by Neil Gaiman, and starring his Dead Boy Detectives.

A brief run by Jerry Prosser and Fred Harper (#80–89) featured a re-reborn Buddy as a white-haired shamanistic figure before the series was canceled after the 89th issue due to declining sales.

In July 2009, DC Comics released a six-issue limited series The Last Days of Animal Man by Gerry Conway and Chris Batista.

In this new timeline, Animal Man is re-established for DC by the creative team of writer Jeff Lemire and artists Travel Foreman and Dan Green.

During his run on the title, Morrison consistently manipulated and deconstructed the fourth wall — the imaginary barrier separating the reader from the setting of the story which also extends to the characters and their creators.

One visual expression of this theme was to present characters in a state of partial erasure — often juxtaposing the artist's pencil drafts with the finished art.

Animal Man ultimately confronts his writer in issue #26, and his family is restored to life, as Morrison cannot justify keeping them dead simply for the sake of "realism".