An impressive body of evidence has suggested that estrogen therapy should be helpful to slow the pathogenesis or progression of atherosclerosis. Estrogen's favorable effects on lipids and endothelial function, coupled with extensive observational epidemiology and data from animal models of atherosclerosis, persuaded many that hormone replacement therapy (HRT) would be helpful for both primary and secondary prevention of coronary disease. Recently, several randomized clinical trials of HRT have been completed, and several more are currently under way. These trials include both primary and secondary prevention cohorts and use clinical as well as anatomic manifestations of atherosclerosis as outcomes. These trials are producing surprising and controversial results that will radically alter contemporary understanding of the role of HRT for cardiovascular disease prevention. This review briefly describes the findings of the Heart and Estrogen/Progestin Replacement Study, the Estrogen Replacement and Atherosclerosis Trial, and other recently completed clinical trials. Trials that are under way are also described and discussed.