Randomized clinical trials have established that lipid- lowering pharmacologic therapy can substantially reduce morbidity and mortality in patients with known coronary artery disease (CAD). Researchers are now working to define the role of lipid-lowering agents in the primary prevention of CAD to extend their benefit to patients at increased risk for future coronary events. The risk assessment models presently used for secondary prevention are not sufficient to identify high-risk, asymptomatic patients. Building on the accumulated data about the physiologic mechanisms and metabolic factors that contribute to CAD, novel serum markers and diagnostic tests are being critically studied to gauge their utility for the assessment of high-risk patients and occult vascular disease. New risk prediction models that combine traditional risk factors for CAD with the prudent use of new screening methods will allow clinicians to target proven risk reduction therapies at high-risk patients before they experience a cardiac event.