The immediate effects of estrogen deficiency are well known and include vasomotor, psychological, and genitourinary symptoms. However, the major importance of the long-term effects of estrogen deficiency, particularly on the skeleton and the cardiovascular system, is now being recognized. Thus, when using hormone replacement therapy (HRT), it is important to consider its effects on osteoporosis and cardiovascular disease as well as on symptom relief. There are several mechanisms whereby HRT can affect the cardiovascular system; these include both metabolic and direct arterial effects. An increased understanding of these mechanisms should allow us to develop optimal HRT regimens for the prevention and treatment of cardiovascular disease in women.