What are the important gender differences seen in men and women with schizophrenia? Although schizophrenia affects men and women with equal frequency, the illness is expressed differently between the sexes. Women with schizophrenia tend to have better premorbid functioning, a later age at onset, a distinct symptom profile and better course of illness, and different structural brain abnormalities and cognitive deficits. Additionally, premenopausal women appear to have a superior response to typical antipsychotics compared to men and postmenopausal women. These gender differences are thought to arise from the interplay between hormonal and psychosocial factors. It has been hypothesized that estrogen, with effects on both neurodevelopment and neurotransmission, may play a protective role in women with schizophrenia and account for some of the gender differences observed in the disorder. Despite the potential benefit of estrogen in this population, women with schizophrenia appear to be at risk for hypoestrogenism, either as a consequence of antipsychotic-induced hyperprolactinemia or, possibly, as a manifestation of the illness itself. The mechanism and consequences of hypoestrogenism in women with schizophrenia, as well as the role for hormonal therapies in this population, require further study.