Psychiatric nosology has at times mirrored cultural mores and societal values, pathologizing behaviors seen at the time to be either immoral or outside the norm. This has been particularly true when it comes to issues related to sexuality and gender. Such pathologizing has resulted in further stigmatization and discrimination in society. Gender incongruence, the experience of an individual whose internal sense of gender is at odds with the sex they were assigned at birth, has long been pathologized. This article will compare the history of the psychiatric depathologizing of homosexuality to the current process of depathologizing gender incongruence.