The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP) issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, five major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. An NCEP working group reviewed the results of these recent trials and assessed their implications for cholesterol management. These clinical trials strongly support the ATP III recommendation that LDL-cholesterol (LDL-C) should be the primary target of lipid-lowering therapy. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of LDL-C 100 mg/dL. In fact, they add to the growing evidence supporting the concept that, for LDL-C in high-risk patients,“the lower, the better” for reducing risk for major cardiovascular events (Figure). Although recent clinical trials focused on drug therapies for LDL lowering, the NCEP update affirms that therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. TLC has the potential to reduce cardiovascular risk through several mechanisms beyond LDL lowering. Recent clinical trials support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm for LDL lowering are presented in the Table 1 and are summarized in Table 2. In high-risk persons, ATP III established that the recommended LDL-C goal is 100 mg/dL; when triglycerides are high (200 mg/dL), a secondary goal is a non–HDL-C 130 mg/dL. According to the update, when risk is very high, an LDL-C goal of 70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, based on available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C 100 mg/dL. For those very high risk patients who have a high triglyceride, a level of non–HDL-C of 100 mg/dL corresponds to an LDL-C level of 70 mg/dL. Identifying a very high risk patient depends on clinical judgment. Examples of such patients include those with established cardiovascular disease plus (1) multiple major risk factors (especially diabetes),(2) severe and poorly controlled risk factors (especially continued cigarette smoking),(3) multiple risk factors of the metabolic syndrome (especially high triglyceride 200 mg/dL plus non–HDL-C 130 mg/dL with low HDL-C [40 mg/dL]) and (4) those with acute coronary syndromes. Moreover, when any high-risk patient has high triglyceride or low HDL-C, consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug.