Compared with men, women are at increased risk of depression, especially at several reproductive-related lifecycle points. This may be partially due to changing levels of estrogen, a hormone that can affect levels of neurotransmitters and neural proteins. As estrogen levels vary throughout the lifespan, risk of depression in women also varies, and not all treatments are appropriate or effective at all times. In adolescence, onset of depression may be associated with onset of puberty, but treating underage girls with antidepressants can risk suicidality. In females of childbearing age, mood disturbances associated with menstrual cycles signal a risk for later full-blown major depressive disorder. In depressed pregnant and postpartum women, risks of treatment versus risks of nontreatment are intricate and require case-by-case evaluation. In perimenopause, vasomotor symptoms may be harbingers of oncoming depression and also may signal the presence of dysregulated hormones and neurotransmitters. Relieving vasomotor symptoms may be a necessary dimension of treating depression. In postmenopause, response to selected antidepressants may depend on whether the patient is also taking hormone-replacement therapy. To attain optimal outcomes, modern psychopharmacologists must tailor treatment of depression to a woman's reproductive stage of life.