Premenstrual syndrome and its most severe form, premenstrual dysphoric disorder (PMDD), are two well-defined clinical entities that affect a considerable number of women. Progesterone metabolites and certain neurotransmitters, such as gamma-aminobutyric acid and serotonin, are involved in the etiology of this condition. Until recently, the only treatment for women with PMDD was psychoactive drugs, such as selective serotonin reuptake inhibitors. Several years ago, there has been evidence of the beneficial role of combined hormonal contraceptives in controlling PMDD symptoms. Oral combined hormonal contraceptives that contain drospirenone in a 24+4-day regimen are the only drugs that have been approved by US Food and Drug Administration for the treatment of PMDD, but there is scientific evidence that other agents, with other formulations and regimens, could also be effective for the treatment of this condition. However, it remains unclear whether the beneficial effect of combined hormonal contraceptives is associated with the type of estrogen or progestogen used or the treatment regimen.