The situation of people with different sexual orientations and gender identities varies worldwide depending on the legal and social situation despite a formal depathologization in the medical classification systems DSM 1973 and ICD 1991. The spectrum ranges from equality to discrimination and exclusion to social ostracism, sometimes combined with legal persecution, in some countries even with the threat of a death penalty. On the basis of a historical overview of the medical-social discourse, it will be shown which scientific and societal advances make depathologization possible, although even in today's times a consistent and sustainable effect of this depathologization appears to be increasingly difficult in some countries, and in some cases even a societal re-pathologization is taking place. Aspects of persistent medical and societal stigma on the health of LGBT (lesbian, gay, bisexual, transgender) people are highlighted. Scientific models that empirically explain the increased risk of mental illness among LGBT people as a result of various forms of stigma and guidelines for psychotherapeutic treatment are presented. In an outlook, the continuing precarious situation of sexual minorities worldwide is pointed out and the importance of medical, social and political destig matization as a prerequisite for the mental health of LGBT people is emphasized. Non-discriminatory legislation is an important element in addition to medical statements and medical guidelines for treatment.