In addition to elevated low-density lipoprotein (LDL) cholesterol, which has been conclusively proven to play a critical role in atherogenesis and coronary artery disease (CAD), other lipoprotein abnormalities are associated with CAD, such as reduced high-density lipoprotein (HDL) cholesterol; increased triglyceride-rich lipoproteins (very low density and intermediate-density lipoproteins); increased lipoprotein(a); small, dense LDL; and LDL with increased susceptibility to oxidation. Other, nonlipid factors such as homocysteine, fibrinogen, C-reactive protein, and soluble cell adhesion molecules may also have a role in risk stratification. The present US treatment guidelines, which focus on LDL cholesterol, stratify risk assessment and intensity of treatment by the presence of CAD; therefore, noninvasive imaging techniques such as ultrafast computed tomography and positron-emission tomography (PET) of the heart, which enable early detection of CAD, are useful in risk assessment. Because the influence of risk factors depends on their severity and combination, global risk assessment provides a necessary guide to the appropriate intensity of treatment. Agents are available that reduce LDL cholesterol and triglyceride and increase HDL cholesterol; although lipoprotein(a), LDL particle size, LDL oxidation, and homocysteine can also be altered, the clinical effects of such alterations are not known. Combination therapy that simultaneously improves multiple components of the lipid profile may provide additional benefit compared with monotherapy. To provide cost-effective treatment to the most patients, high-risk patients must be identified through systematic screening. Then each patient should be treated with the most cost-effective agent(s) that will enable achievement of the lipid levels recommended in the guidelines.