Hormone replacement therapy has previously been recommended for the prevention and treatment of many conditions affecting women as they age. Decades of research have determined many beneficial biologic effects of hormones on the direct and indirect mechanisms of atherosclerosis. Observational studies have furthered the enthusiasm for hormone use with estimates of 35-50% reduction in risk for future cardiovascular events in women who took estrogens at menopause. However, there may be inherent selection and compliance biases in the non-randomized cohort methodology. The last decade has produced important randomized clinical trial results which now question whether estrogen replacement will reduce risks or even potentially increase cardiovascular event rates, particularly in women with known coronary disease within the first 1-2 years of initiating treatment. Conclusive evidence of the true risk:benefit ratio for hormone use after menopause awaits the completion of ongoing clinical trials. Until those results are available, each decision for postmenopausal hormone use must be made on a case-by-case basis weighing individual risks with the positive and negative aspects of therapy.