Although important in reducing atherosclerosis progression and cardiovascular events in women, lowering of low-density lipoprotein cholesterol levels is not sufficient for optimum prevention. Additional potential targets for intervention include reducing levels of triglyceride-rich lipoproteins, increasing high-density lipoprotein cholesterol, and replacing certain hormones that decrease during menopause. Hormone replacement therapy (HRT) for the reduction of atherosclerosis progression and cardiovascular events has become complicated because of conflicting outcomes from recent surrogate end point studies and secondary prevention randomized clinical trials. The key to HRT may be early intervention, when women first enter menopause and the atherosclerotic process appears to be relatively quiescent. Although many questions remain to be answered in this important area of women's health, there is a fact that is certain: administration of HRT for the reduction of cardiovascular events is not a straightforward proposition. Powerful imaging tools for monitoring atherosclerosis progression exist that can be used to help address many questions relating to type, dose, regimen, and timing of HRT.