Hormone replacement therapy aims to protect against osteoporosis and alleviate fastidious menopausal symptoms such as hot flushes, depression, sleep disturbances and vaginal dryness. In view of the acknowledgement of estrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, hormone replacement therapy may also be proposed as a substantial beneficial cardioprotective agent. The effects of progestins on lipoprotein profile and vasomotor tone are dependent on the chemical structure and the scheme of administration of progestins, with androgenic progestins and cyclical therapy having a potential detrimental effect. Prospective primary and secondary prevention studies, however, suggest that the adjunct of non-androgenic progestins to estrogen therapy is at least as effective as estrogen replacement therapy in reducing cardiovascular mortality and morbidity. Data from recent randomized secondary prevention studies have to be viewed with caution.