Cardiovascular disease, primarily coronary heart disease (CHD), outnumbers the next 16 causes of death in women combined. However, the long-held belief that heart disease in women has a more benign prognosis than in men has resulted in less aggressive diagnosis and management patterns. Appreciation of the differences between men and women in CHD risk factors and presentation can assist in treatment decisions. Although estrogen replacement offers substantial beneficial effects on lipid levels in postmenopausal women, the first 2 randomized trials of estrogen alone and estrogen plus progestin, the Heart and Estrogen/Progestin Replacement Study and Estrogen Replacement and Atherosclerosis Study, observed no benefit in reducing risk of CHD death and nonfatal myocardial infarction and angiographic progression of CHD, respectively, in women with CHD. Available data show that lipid-lowering therapy reduces women's CHD risk and mortality but also indicate that a considerable proportion of women remains untreated or undertreated. Randomized trials of statins for primary and secondary prevention of coronary heart disease suggest that these agents are at least as effective for lowering coronary disease risk in women as in men. Therefore, statin drugs should be the drug of first choice for women with established CHD. Hypercholesterolemic postmenopausal women who require estrogen for menopausal symptoms may derive further reductions in low-density lipoprotein cholesterol and reductions in trigyceride levels with the addition of a statin drug.