Recently, there has been considerable discussion about the benefits and risks of using hormone replacement therapy (HRT) for cardiovascular protection in postmenopausal women. Numerous studies have addressed this issue, with conflicting results. Observational studies strongly suggest a benefit of HRT for primary prevention of cardiovascular disease (CVD), whereas controlled trials that tested a single common regimen of estrogen plus progestin found no effect on CVD events or angiographic progression in older women with established CVD. More recently a primary prevention trial in high risk patients found reduced carotid atheroma with estrogen alone. A variety of combination therapies with various estrogens and progestins are now available. These formulations have significantly different effects on cardiovascular risk markers, which independently affect outcomes. This information should be considered when deciding whether to use HRT in an individual woman, and if so, which formulation to use.