The perception that menopause leads to mood disturbances such as depression has a long history. How did these beliefs come about, and are they supported by the scientific literature? This article reviews the theories of menopause and depression, the scientific literature, and the implications of these findings for prevention and treatment. Epidemiologic studies of menopausal status and depression do not provide consistent evidence of an association between the menopausal transition and depression among the general population of women. Depression experienced by women transitioning through menopause may be attributed to factors unrelated to menopause. A subset of women, however, may be more vulnerable to the effects of hormonal changes. For some women, short-term estrogen replacement therapy to relieve vasomotor symptoms may be beneficial, although for others psychotherapy or antidepressants may be more appropriate. Additional research is needed to better understand the association between different stages of the menopausal transition and dysphoric mood or depression, and better identification of women potentially at risk for depression during the menopausal transition.