Cardiovascular disease is the leading cause of death in postmenopausal US women. The contribution of postmenopausal hormone replacement therapy to cardiovascular risk is one of the most controversial women's health topics. Strikingly discordant results, between observational and randomized clinical trials, have been reported. Remaining questions regarding time of hormone therapy initiation are discussed, as are ongoing trials focused on these questions. Cardiovascular concerns, cautions, and current recommendations for use are delineated.