Women younger than 50 have a lower age-specific incidence of CVD than men. With advancing age this difference gradually disappears. These well-established facts provide the rationale for numerous primary and a few secondary intervention studies with ERT. With increasing sophistication and longer observation periods, both case-control and cohort studies agree on a cardioprotective effect by estrogens. A meta-analysis suggests that estrogens halve the risk of myocardial infarction (MI). As observational studies do not control exposure, confounders and biases may be present. Even when considering the most pessimistic scenario, however, the clinical significance for preventing MI by ERT would still be substantial; albeit insufficient data from a clinical trial agree on a markedly reduced risk for MI. Some of the primary prevention trials are large enough to permit analysis of subgroups. In women carrying risk factors for CVD, the cardioprotective effect appears to be augmented. Such risk factors comprise smoking, hypertension, and perturbed serum lipids. In women who have already had MI, the relative risk may be as low as 0.2 for those treated with ERT. While there are compelling epidemiologic data to suggest cardioprotection by ERT, the epidemiology on combined therapy and CVD is scanty. However, there is no epidemiological evidence to suggest a reduced cardioprotection by progestogen co-medication, but further data are urgently needed in support of this notion.