Cardiovascular disease has emerged as a leading cause of death in women. In recent years, significant attention has been paid to the potential benefits of hormone therapy on chronic diseases such as cardiovascular disease. Large prevention trials failed to confirm the cardioprotective effect of estrogen. The divergent findings from observational and randomized clinical studies are summarized and reasons for the different results are postulated. Use of estrogen alone or estrogen opposed with progestins is not indicated for the prevention of cardiovascular disease and may even increase the risk of stroke. Oral estrogen increases venous thromboembolism events. Recent data suggest that transdermal estrogens are safe with respect to venous thromboembolism. Current data have limited ability to investigate the wide variety of hormone treatments available. Clinical research should be continued to assist patients and clinicians in making treatment decisions on the basis of an individual's benefits and risks.