To review the diagnosis, therapeutic options, and potential complications of treatment of transsexualism.We summarize the appropriate initial assessment and the current guidelines for hormonal and surgical treatment of patients with transsexualism.The cardinal feature of transsexualism is the permanent feeling of gender dysphoria. As part of the treatment of this condition, patients may seek medical and surgical therapies to change their physical appearance to match their internal gender identity. Cross-sex hormone therapy is a key medical management and is often prescribed in consultation with an endocrinologist. Patients should participate in a period of psychotherapy before such hormonal therapy is initiated. Medical therapies for transsexualism are associated with potentially serious complications, such as thromboembolism related to estrogen treatment and testosterone-induced hepatotoxicity. Patients should be carefully selected for therapy with use of the current management guidelines published by the Harry Benjamin International Gender Dysphoria Association.Physicians caring for patients with transsexualism should have a general knowledge about the diagnosis, available treatment, and monitoring for complications of hormonal therapy. Ongoing research and education are necessary for improvement in the health care of these patients.