The focus of this chapter is the relationship between the onset of depression in women and the reproductive events of the menopause transition. Epidemiologic studies have documented that the majority of women do not become depressed during the menopause transition. However, recent longitudinal studies suggest that in some women, the reproductive events related to the menopause transition could play a role in the onset of depression. No abnormality of ovarian hormones has been identified that distinguishes women with depression from those who remain asymptomatic during the menopause transition. Nonetheless, several findings suggest a role of ovarian hormones in the onset of these depressions. First, episodes of depression cluster during the stage of the menopause transition that is accompanied by estradiol withdrawal. Second, randomized controlled trials have documented the short-term (3-6 weeks) antidepressant efficacy of estradiol in depressed perimenopausal women. Third, experimentally induced estradiol withdrawal triggers mood symptoms in some women. Thus, although depression is not a uniform accompaniment of the menopause transition, in some women, age-related changes in ovarian estrogen production may alter central nervous system function and predispose them to develop depression.