Existing guidelines for primary prevention have not achieved their objective of controlling risk factors, such as hypertension and hyperlipidemia. Only 36.8% of patients with hypertension in the United States have their blood pressure controlled to current guidelines, only a minority of patients have controlled LDL to current recommendations, and a very low percentage have both blood pressure and cholesterol controlled. In 1 study, <10% of patients achieved both goals (<5% of black women). Reasons for this include lack of awareness, complexity of guidelines, and skepticism regarding their applicability to individual patients. In addition, the current approach to risk factors has the important limitation that it does not consider the individual as a whole. Risk varies widely depending on the presence of additional risk factors, and individuals who develop cardiovascular events have modest increases in >1 risk factor. In the Multiple Risk Factor Intervention Trial (MRFIT), the majority of coronary heart disease (CHD) events (64% to 100% of fatal CHD and 46% to 88% of nonfatal myocardial infarctions) occurred in patients (347,978 men aged 35 to 57 years) with ?? major risk factors. In general, the relative risk reduction of lipid lowering and antihypertensive therapy is similar for those with or without additional risk factors. Therefore, the benefit (absolute risk reduction) of therapy is higher and the number needed to treat to prevent 1 event is lower in those with higher global risk, usually those with >1 risk factor. Multidimensional intervention based on what we know today is necessary to achieve the lowest possible event rate in primary prevention. New clinical trials showed that targeting >1 risk factor accrued higher benefits. Similarly, assessing health care quality on only 1 risk factor, rather than global risk, is not optimal. It has been estimated that prescribing statins to patients with high global risk regardless of cholesterol level would result in the avoidance of more events than treating only those with high cholesterol. Approaches to prevention based on combined modulation of common risk factors of coronary artery disease may result in a very large decrease in disease burden. Dr. Roberts stated that statin drugs are to atherosclerosis what penicillin was to infectious diseases. We must not forget that penicillin does not cure all infectious diseases and LDL lowering does not eliminate the risk of stroke, end-stage renal disease, heart failure, or even myocardial infarction.