Among postmenopausal women, 38% use hormone replacement therapy (HRT)— the leading brand of conjugated equine estrogen is the second most prescribed drug in the United States. Although adverse effects of this therapy have been recognized, it was traditionally reasoned that HRT could be broadly recommended to postmenopausal women because coronary heart disease was their most significant health risk. Evolving vascular biologic understanding, however, suggests that HRT, in direct opposition to the existing observational study data, does not reduce coronary heart disease risk. During the summer of 2002, three important studies on HRT dramatically changed our view of this widespread treatment. These trials provide clear, new, guidelines for patients and physicians contemplating HRT therapy.