Transsexualism is considered to be the extreme end of the spectrum of gender identity disorders characterized by, among other things, a pursuit of sex reassignment surgery (SRS). The origins of transsexualism are still largely unclear. A first indication of anatomic brain differences between transsexuals and nontranssexuals has been found. Also, certain parental (rearing) factors seem to be associated with transsexualism. Some contradictory findings regarding etiology, psychopathology and success of SRS seem to be related to the fact that certain subtypes of transsexuals follow different developmental routes. The observations that psychotherapy is not helpful in altering a crystallized cross-gender identity and that certain transsexuals do not show severe psychopathology has led clinicians to adopt sex reassignment as a treatment option. In many countries, transsexuals are now treated according to the Standards of Care of the Harry Benjamin International Gender Dysphoria Association, a professional organization in the field of transsexualism. Research on postoperative functioning of transsexuals does not allow for unequivocal conclusions, but there is little doubt that sex reassignment substantially alleviates the suffering of transsexuals. However, SRS is no panacea. Psychotherapy may be needed to help transsexuals in adapting to the new situation or in dealing with issues that could not be addressed before treatment.