Epidemiologic studies have shown that the prevalence of depression is about twice as high in women than in men. Both neurobiologic and psychosocial factors may contribute to this difference. Gender differences in depression have also been noted with regard to symptom presentation, comorbid disorders, course of illness, and response to treatment. This article provides an overview of gender differences in the phenomenology and treatment of depression, particularly the effect of gender on antidepressant treatment response. Clinicians should consider gender as a factor in both the assessment and treatment of depression.