This chapter focuses on women's mental health issues as they relate to depression. Specifically, women are at more risk than men for developing depression throughout their lifetimes, especially during their childbearing years. The incidence of depression in women rises during puberty. High-risk periods for onset or recurrence of a major depressive episode include the postpartum period and the perimenopausal transition to menopause. This chapter discusses how fluctuations of estrogen levels may be linked to the onset or recurrence of a major depressive episode in a woman, and provides some tips for how to manage depression in women, including evolving findings about treatment of vasomotor symptoms associated with the onset or recurrence of depression during perimenopause.