In the summer of 2004, an evidence-based update of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines for management of hypercholesterolemia was published. This detailed assessment of 5 major clinical trials, published since the ATP III report in 2001, was designed to provide guidance for physicians in decision making for patients at high risk and very high risk. We have tried to summarize this assessment by suggesting the following to clinicians: (1) Calculate global risk of coronary artery disease (CAD) to determine an overall strategy for cholesterol management. (2) Emphasize the benefits of diet, exercise, and weight control or therapeutic lifestyle change, especially in those with lifestyle risk factors. (3) Use 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors (statins) as first-line drugs to reduce risk of CAD and stroke in those at moderate to high risk. (4) If statins are prescribed, use moderate doses that reduce plasma levels of low-density lipoprotein (LDL) cholesterol by > or = 30% to 40%. (5) Strongly consider statin therapy in those with diabetes (with the exception of severe hypertriglyceridemia). (6) Consider LDL cholesterol-lowering drug therapy for lipids in older patients at risk. (7) Consider adding either a fibrate or nicotinic acid in high-risk patients with elevated plasma triglyceride values or low levels of plasma high-density lipoprotein cholesterol after statin therapy has achieved the LDL cholesterol goal. (8) Continue to treat those at low risk in similar fashion as before. This update is to inform current physician judgment in this area. Further clinical trial data that may modify or extend these recommendations are eagerly awaited.