Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome, causing a marked reduction in the quality of life for about 5% of all women of fertile age. The cardinal symptoms are irritability and anger, which surface regularly between ovulation and menstruation and disappear completely within a few days after the onset of menstruation. Other frequent symptoms are depressed mood, affect lability, tension, and carbohydrate craving. In placebo-controlled trials, the serotonin reuptake inhibitors (SRIs) clomipramine, fluoxetine, sertraline, paroxetine, and citalopram have proven very effective for PMD, with a response rate of 60% or higher; in contrast, nonserotonergic antidepressants are not effective. The onset of action of SRIs is rapid, allowing for intermittent administration during luteal phases only. The impressive effect of SRIs for PMD is probably not equivalent to the antidepressant effect of these drugs, but is more likely to be a manifestation of the well-established influence of serotonin on aggression and irritability. It strongly reinforces the assumption that a major function of serotonergic neurons in the brain is to modulate sex-steroid—driven behavior.