Sex steroids play a very important role in female neurobiology. Postmenopausal gonadal hormone withdrawal seem to be of critical importance in mood disorders, reduced libido and cognitive disturbances, which accompany this phase of a woman's life. Clinical studies have demonstrated that central nervous system (CNS) effects of estrogens are not only limited to resolution of vasomotor instability, they are extended to psychological disturbances like depression, behavioral changes and cognitive dysfunction. Progestins, on the other hand, may have variable effects on the brain, occasionally inducing dysphoric mood and altered behavior. Although their use in hormone replacement therapy (HRT) is widely debated, androgens may help resolve changes in libido experienced by many women after the menopause. It is still, however, difficult to draw guidelines on the use of HRT and postmenopausal CNS disorders as studies present up to date have been carried out with different kinds of molecules and routes of administration. Further studies are required in order to explain the specific role of endogenous and exogenous sex steroids on the CNS.