Nearly 250,000 women die each year from cardiovascular disease, making it the leading cause of death in women. The initial clinical manifestation of coronary artery disease (CAD) in women is usually 10 years later than in men on average, with the first myocardial infarction presenting 20 years later. At any age the prevalence of CAD is lower in women, but with advancing age, this gender differential diminishes. The fact that CAD prevalence is lower in women has led to the false presumption that women are protected from cardiovascular diseases. Since women live 8 to 10 years longer than men, the absolute number of deaths from cardiovascular disease (CVD) exceeds that of men. Although there has been a decline in the overall number of cardiovascular deaths, the coronary incidence has been increasing in women and decreasing in men. Contrary to belief, CAD causes far more deaths in women than does cancer (Figure 1). Consider the statistics: approximately 1 out of 3 women will die of a cardiovascular event; more than a half-million women die of CVD each year; one women dies of CVD almost each minute in the United States; and two-thirds of the women who die suddenly have no previously recognized symptoms. Advances in diagnosis and treatment of CVD appear to have translated into a survival benefit in men but not in women. The mortality due to CVD remains high in women, with no improvement in survival trends over time compared to men (Figure 2). This may be related to differences and delays in recognizing CVD in women or in treatment strategies, and to biological differences. Women with acute coronary syndrome often delay calling for professional help and present more frequently with atypical symptoms, such as abnormal pain locations, nausea, vomiting, fatigue, and dyspnea. Women not only present later from the onset of chest pain but are also sicker at the time of diagnosis. Furthermore, there appears to be a bias against heart disease in women - both patients and their caregivers/health care providers do not recognize or treat CVD in a timely manner in women. Compared to men, women are less likely to receive appropriate treatment for heart disease such as optimal control of blood pressure, use of aspirin, cholesterol-lowering medications, thrombolytics, or referrals for interventions such as balloon/ stent or bypass surgery. Women seem to be evaluated less intensively, and referrals for cardiac catheterization are 8-fold higher in men than in women. The clinical outcomes including myocardial infarction mortality, all-cause mortality, and reinfarction rates are worse in women with CVD than in men. Many risk factors contribute to CAD in women, but menopause is one of the strongest. Risk of CAD in postmenopausal women is 40 to 50% higher than in premenopausal women, and hormone replacement therapy (HRT) increases the risk. This paper discusses the myriad risk factors for CAD in women and explores the relationship between CAD and hormone replacement therapy in postmenopausal women.