Multiple observational studies suggest a marked reduction in risk of coronary heart disease (CHD) associated with postmenopausal estrogen use. A new meta-analysis presented here extends these results to estrogen plus progestin regimens. Although the findings from observational studies are strong and consistent, and there are several plausible mechanisms by which estrogen might reduce risk for CHD, most of the known biases would tend to exaggerate estrogen's benefit. Further, estrogen therapy clearly increases risk for endometrial hyperplasia and cancer, venous thromboembolic events and gallbladder disease, and long-term use probably also increases the risk of breast cancer. Therefore, until findings from randomized trials confirm and quantitate the benefit of estrogen therapy for prevention of CHD, we believe it should not be recommended to all postmenopausal women.