Cardiovascular disease is the leading cause of mortality in women, a fact that is underappreciated by women and physicians. Clinical and experimental data underscore the cardioprotective effects of female sex hormones, particularly estrogen. Indeed, the loss of female sex hormones after menopause contributes to the striking increase in the incidence of cardiovascular morbidity and mortality after menopause. Estrogen replacement therapy improved lipoprotein profiles in the postmenopausal women, but this accounts for less than half of the cardioprotective effects of estrogen replacement therapy. Addition of progestins to estrogen therapy in women appears not to significantly attenuate the cardioprotective effects of estrogen replacement therapy despite experimental data suggesting otherwise. This review addresses potential mechanisms, other than influences on lipoproteins, by which estrogen and progesterone exert their cardiovascular protective effects. Particular emphasis is directed to genomic and nongenomic effects of estrogen and progesterone that are exerted directly on cardiovascular tissue.