Cardiovascular diseases (CVD) remain the major cause of death in postmenopausal women. Before menopause, women are relatively protected from ischemic heart disease and thromboemolism by their circulating estrogens, but this protection is lost after menopause. Following menopause, adverse lipid changes occur and the levels of several coagulation factor increase. One of the major predisposing factors for CVD is the metabolic syndrome, including myriad risk biomarkers: abdominal girth, blood pressure, fasting glucose, triglycerides, lipids. In many ways, the metabolic syndrome is a precursor to the development of abnormalities of insulin action and diabetes. In parallel, there are effects upon blood coagulation and fibrinolysis. Common preventive therapies require rigorous evaluation. Hormone replacement therapy (HRT) has not produced the expected reduction in CVD and the ideal HRT is probably unobtainable. For long-term HRT users, the risk of thromboembolism needs to be weighed against probable benefits. With respect to the effects of HRT, oral estrogen is associated with elevation in C-reactive protein and varied effects on IL-6, but transdermal estradiol has no significant effect on these parameters. Despite the varied effects of HRT on inflammatory biomarkers, there is no definitive evidence that change in these markers results in modification of cardiovascular risk.