Cardiovascular disease remains the number one killer of women. Although important for the reduction of cardiovascular events, lipid alteration does not appear to be sufficient to obtain optimum reduction in cardiovascular risk. Women have a potential opportunity for further reduction in cardiovascular risk through postmenopausal hormone replacement therapy. More than 50 observational studies indicate that postmenopausal use of hormone replacement therapy reduces atherosclerosis and cardiovascular events. However, recently reported, randomized, controlled clinical trials have yielded mixed results as to whether hormone replacement therapy reduces cardiovascular events relative to placebo. These, as well as other randomized controlled trials of hormone replacement therapy and cardiovascular disease in postmenopausal women, are reviewed. Although conclusions concerning the specific hormones used in the specific populations studied can be offered from the completed trials, more broad conclusions concerning the use of hormone replacement therapy in the prevention of cardiovascular disease will have to await conduction and completion of other trials.