Cardiovascular disease is the leading cause of mortality in postmenopausal women in developed countries. A possible cardioprotective role of hormone replacement therapy (HRT) is suggested by epidemiologic studies of HRT and reduced risk of coronary heart disease, as well as by randomized trials of HRT and lipid subfractions. Estrogen has beneficial effects on the lipid profile, raising high-density lipoprotein cholesterol levels and reducing low-density lipoprotein cholesterol levels each by approximately 10%. Other possible biologic mechanisms include beneficial effects on vascular function, oxidative status, endothelial-dependent vasodilation, intimal hyperplasia and insulin sensitivity. Estrogen's net effects on coagulation and fibrinolysis are less clear. Estrogen replacement therapy is associated with decreased atherosclerosis in several animal models. However, most of the available data on HRT derive from observational studies or small randomized trials assessing biologic intermediates rather than clinical events. Further research, including large-scale randomized clinical trials, are required to evaluate definitively the role of estrogen replacement therapy, especially given uncertainties about the effects of combined estrogen-progestin therapy and the balance of benefits and risk of this common intervention in postmenopausal women.