It is well documented that women are twice as likely as men to be diagnosed with depression, but recent data suggest that gender differences also must be considered in the treatment of depressed patients. Specifically, depression in women may have a different longitudinal course and has been associated with a less successful treatment outcome. Several possible explanations are explored here. First, there appear to be gender differences in pharmacokinetics and responsiveness to medication. Second, depressed women have higher rates of psychiatric and medical comorbidity than depressed men. Third, normal hormonal changes may serve as triggers for psychiatric illness in genetically vulnerable women. Finally, women are subject to unique psychosocial stressors that can impede recovery if not addressed. These data indicate that our approaches to treating women with depression need to be modified. This report concludes with a list of integrated strategies designed to meet the treatment needs of these patients.