This chapter discusses the symptoms that occur repeatedly in association with the menstrual cycle and during the menopause transition (MT). Several studies have refuted the hypothesis that premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) is associated with abnormalities in circulating ovarian hormones. Antidepressant medications with primary serotonergic action, such as the selective serotonin reuptake inhibitors (SSRIs), have become the mainstay of pharmacological treatment of PMDD, with proven safety and efficacy. Given that women with PMDD are more sensitive to the normal hormonal fluctuations of the menstrual cycle, several trials have been conducted to examine whether manipulation of the female sex hormones could lead to an effective treatment of PMDD. Prospective studies have consistently shown that during MT women are at higher risk to develop depressive symptoms and/or to meet criteria for major depressive disorder (MDD). Antidepressants remain the first choice for the management of depression in any given age/reproductive staging group.