The comic began on December 1, 2001 as an isolated series of jokes with a transgender theme. The current storyline began December 31st of that year. Venus Envy is about the life of Zoë Carter, a young transsexual girl living in Salem, Pennsylvania. She is forced to relocate from her previous home in Punxsutawney and attend a new school due to transphobic harassment. The comic was described by Washington Blade as a "compelling, sometimes moving teen soap opera."