It is well documented that coronary heart disease (CHD) is the leading cause of death in women-especially postmenopausal women. The role of hormone replacement therapy (HRT) in prevention of CHD has been considered for many years. Early epidemiological studies suggested estrogen to have a potential cardioprotective role, noting that premenopausal women have a decreased risk of developing CHD compared with men. Later observational studies showed decrease of CHD risk in postmenopausal women on HRT. By 1996, estrogen (specifically Premarin) was one of the most dispensed medications in the United States. Major medical organizations such as the American College of Physicians and American College of Obstetricians and Gynecologists widely endorsed and encouraged HRT for CHD risk reduction, along with using HRT for other potential benefits (such as osteoporosis prevention). Unfortunately, recent clinical trials seem to raise more questions than provide definitive proof in the protective role of estrogen in CHD. A review of recent and ongoing observational studies and clinical trials may help guide physicians in their recommendation and discussion of the role of HRT in postmenopausal women. As this article was being prepared for publication, reports from both the Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II) and the Women's Health Initiative (WHI) were published. Both studies concluded that HRT has no role in primary or secondary prevention of CHD in women.