Psychosis, mainly schizophrenia, is a heterogeneous disorder with a great variability in its clinical presentation. This heterogeneity may be explained by the role of gender; thus a gender-based approach could help us to better define the disease. Gender differences in social functioning, age of onset, course of the illness, and other domains have been described by several authors, showing better functioning and improved outcome in women with schizophrenia. Moreover, several treatments are gender sensitive, with differences in treatment response depending upon gender. The estrogen hypothesis is one of the most interesting explanations for this gender difference. Estrogens could be useful for understanding the pathophysiology of the illness or tailoring specific genderrelated treatments.