Coronary heart disease is a highly prevalent and lethal illness for women, particularly in their menopausal years, a fact that fostered interest in hormone use for cardioprotection. Despite the compelling evidence of cardiovascular benefit of estrogen therapy and estrogen and progestin therapy in observational studies of postmenopausal women, and multiple biologically plausible mechanisms for estrogen benefit, precise clinical outcome information from prospective randomized controlled trials is lacking. The only such trial reported, the Heart and Estrogen/Progestin Replacement Study, not only failed to demonstrate cardioprotection, but showed an early adverse outcome in women with documented coronary heart disease who received daily conjugated equine estrogen and medroxy-progesterone acetate. Several large randomized clinical trials of hormone and selective estrogen receptor moderator therapy for primary and secondary prevention are currently underway.