Evidence that CHD morbidity and mortality can be reduced with reduction of LDL-C to less than 100 mg/dL (2.6 mmol/L) is rapidly accumulating. NCEP-ATP III guidelines should be considered minimal goals of therapy. Regarding the prevention and treatment of CHD, health care providers need to recognize the wide therapeutic gap between evidence-based medicine and customary clinical practice. Aggressive pharmacologic therapy is probably required to achieve optimal LDL-C levels in many hyperlipidemic patients. Novel agents, including selective cholesterol absorption inhibitors, will provide clinicians with a tool to safely and effectively target the exogenous pathway of cholesterol metabolism. Combination therapy with cholesterol-lowering agents that have complementary mechanisms of action and can be safely co-administered may be a new option to achieve broader lipid control.