Cardiovascular disease is rare in premenopausal women compared with men in similar age groups. After menopause, however, the gender difference in cardiovascular disease diminishes, and there is an increased incidence of coronary risk and events in women. Although a number of factors contribute to the development of atherosclerotic disease in women, estrogen replacement therapy reduces cardiovascular risk. Potential molecular mechanisms for the antiatherosclerotic effects of estrogen are discussed here. It is proposed that lipid-lowering and antioxidant properties of estrogen synergize to elicit the observed vasoprotective effects. These processes are discussed in the context of balloon-injury models and hypercholesterolemia.