Andrews' novels combine Gothic horror and family saga, revolving around family secrets and forbidden love (frequently involving themes of consensual incest, most often between siblings), and they often include a rags-to-riches story. Her most well-known novel is the infamous bestseller Flowers in the Attic (1979), a tale of four children locked in the attic of a wealthy Virginia family by their estranged religious grandmother for over three years.
Her novels were so successful that after her death her estate hired a ghost writer Andrew Neiderman, to write more stories to be published under her name. In assessing a deficiency in Andrews' estate tax returns, the Internal Revenue Service argued (successfully) that Andrews' name was a valuable commercial asset, the value of which should be included in her gross estate.