Observational studies reveal a cardioprotective effect of hormone replacement therapy. The precise mechanisms whereby this treatment influences disease risk are not fully understood. Much attention has been paid to changes in lipid and lipoprotein metabolism, but this explains only part of the protective effect. In this short review, the roles of monocyte and platelet function in atherogenesis and thrombus formation are discussed. It is shown that hormone replacement therapy favourably down-regulates monocyte and platelet reactivity, which may be important in explaining the beneficial effect on the risk of cardiovascular disease.