Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome afflicting 5% to 10% of all fertile women. Cardinal symptoms--appearing regularly between ovulation and menstruation and disappearing within a few days after the onset of the bleeding--are depressed mood, tension, affect lability, and irritability. Of these symptoms, irritability is often the most prominent. Serotonin reuptake inhibitors (SRIs), but not nonserotonergic antidepressants, reduce the symptoms of PMD effectively. The onset of action of SRIs is much shorter when used for PMD than when used for depression, enabling women with PMD to restrict medication use to the luteal phase of the cycle (so-called intermittent treatment). The findings that SRIs are effective for PMD--and that sexual dysfunction is the most frequent side effect during long-term treatment--both lend support for the hypothesis that a major role for brain serotonin is to modulate sex steroid-driven behavior.