Premenstrual dysphoric disorder (PMDD) comprises emotional and physical symptoms and functional impairment that lie on the severe end of the continuum of premenstrual symptoms. Women with PMDD have a differential response to normal hormonal fluctuations. This susceptibility may involve the serotonin system, altered sensitivity of the GABA_A receptor to the neurosteroid allopregnanalone, and altered brain circuitry involving emotional and cognitive functions. Serotonin reuptake inhibitors are considered the first-line treatment. Second-line treatments include oral contraceptives containing drospirenone, other ovulation suppression methods, calcium, chasteberry, and cognitive-behavioral therapy.