OBJECTIVE: The purpose of this article is to review the literature concerning gender differences in the course of bipolar illness and discuss issues relevant to the treatment of women with the illness. METHOD: The literature concerning the following topics is reviewed: gender differences in the course of bipolar illness; effects of the female reproductive cycle on the course of bipolar illness; special considerations in the treatment of bipolar women (focusing on the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes); and hypotheses to explain the greater prevalence of rapid cycling among bipolar women than among bipolar men. RESULTS: Data clearly indicate that rapid cycling is more common among bipolar women. Data also suggest that bipolar women may have more depressive episodes (and fewer manic episodes) and may be more likely to suffer from mixed (as opposed to pure) mania than bipolar men. While it is clear that bipolar women are at high risk for postpartum episodes, the effects of other reproductive system events (i.e., puberty, menstrual cycle, pregnancy, menopause, use of oral contraceptives or hormone replacement therapy) on the course or treatment of bipolar illness have received little systematic study. It is unclear whether women are at higher risk than men for developing lithium-induced hypothyroidism. Higher rates of hypothyroidism, greater use of antidepressants, and gonadal steroid effects are possible explanations for the greater prevalence of rapid cycling among bipolar women. CONCLUSIONS: Gender differences in bipolar illness and the effects of the female reproductive system on the course and treatment of the illness deserve more study. The importance of a longitudinal approach to these questions is emphasized.