Recent primary and secondary intervention studies have shown that reduction of low-density lipoprotein cholesterol (LDL-C) with statins significantly reduced coronary heart disease (CHD) morbidity and mortality. However, many patients with dyslipidemia who have or are at risk for CHD do not reach target LDL-C goals. The recently updated National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines identify a group of patients at very high risk for CHD for more aggressive LDL-C reduction and reaffirm the importance of high-density lipoprotein cholesterol (HDL-C) by raising the categorical threshold to 40 mg/dl. Lipid-lowering therapy needs to be more aggressive in both primary and secondary prevention settings, and therapy should be considered to increase HDL-C as well as lower LDL-C in order to improve patient outcomes. Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum.