Based on the established relation between low-density lipoprotein (LDL) cholesterol and coronary artery disease (CAD), the treatment guidelines of the US National Cholesterol Education Program (NCEP) focus on LDL cholesterol reduction for primary and secondary prevention of CAD events. Abundant clinical trial evidence supports the importance of LDL cholesterol-lowering in decreasing CAD risk, both in angiographic trials, which measure CAD progression, and in trials with morbidity and mortality endpoints. The LDL cholesterol targets in the guidelines remain important treatment goals, and ongoing trials should answer questions of whether further reduction in LDL cholesterol will provide much additional benefit. Even in trials of statin therapy, in which substantial reductions of LDL cholesterol have been obtained, statins decrease (by 23-37%) but do not entirely eliminate events, suggesting that lipid parameters besides LDL cholesterol, such as high-density lipoprotein (HDL) cholesterol, triglyceride, lipoprotein(a), and LDL particle size and susceptibility to oxidation, as well as other risk factors, influence CAD risk. Unfortunately, at present, the majority of high-risk patients are not receiving either diet or drug therapy. Systematic screening to identify high-risk patients and methodical follow-up to implement diet, lifestyle modification, and drug therapy to lower LDL cholesterol, as provided for in the NCEP guidelines, should lead to significant benefits in the prevention of CAD events.