Gail Simone is well known among the comic book community for coining the term Women in Refrigerators and writing the original list. She began a weekly column, entitled "You'll All Be Sorry!", which she updated regularly for two years. After scripting contributing several stories for The Simpsons, she entered superhero comics penning Deadpool and it's successor, Agent X, for fifteen issues. She began her five-year run on Birds of Prey with issue #56, and continued until issue #108, with a rotating team of artists.

When her long run on Birds of Prey was finished, she began an eight issue run on Action Comics with John Byrne, where she introduced Livewire into comic continuity. She subsequently wrote a six-issue miniseries called Villains United that tied heavily into the Infinite Crisis, and its sucessor, the six issue miniseries Secret Six.

With some ideas from Grant Morrison, Gail Simone invented the new Atom character, Ryan Choi. After eighteen issues, she left the title and started writing Wonder Woman from issue fourteen. Gail Simone has teamed up with Nicola Scott again to write a new Secret Six ongoing series.