Although women have a greater life expectancy than men and tend to develop coronary artery disease (CAD) 10 to 20 years later than men, the burden of CAD in women is high, with a lifetime risk >20%. Beginning at puberty, women have more favorable lipoprotein profiles than men. High-density lipoprotein (HDL) cholesterol levels remain higher in women than men throughout their lifetime. Low-density lipoprotein (LDL) cholesterol levels in women exceed those in men after middle age, but despite a shift toward smaller, denser LDL particles at the time of menopause, LDL particle number remains lower in women than in men throughout the lifespan. Lipoprotein levels strongly predict incident and recurrent CAD events in both sexes, and LDL particle size may be a better predictor of premature CAD in women than of CAD associated with advanced age. The effects of postmenopausal hormonal therapy on lipoprotein levels are complex, and the benefits of such therapy are not established. In contrast, lifestyle changes and pharmacological lipid-lowering therapy have been shown to favorably influence the natural course of atherosclerotic disease and reduce cardiovascular events in men and women.