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The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines call for more aggressive lowering of low-density lipoprotein cholesterol (LDL-C) and will substantially increase the number of patients eligible for lipid-lowering therapy. Statins, the current treatment standard, have proven to be highly efficacious in lowering LDL-C and reducing coronary heart disease (CHD) risk. Because some patients are unable to tolerate 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) or they are not candidates for statin therapy, however, other cholesterol-lowering modes of therapy are needed. Currently available nonstatin drugs often do not reliably reduce LDL-C to a desired extent or are limited in their safety and tolerability. Ezetimibe, a novel lipid-lowering agent until recently in phase III development, is the first in a new class of selective cholesterol absorption inhibitors and offers a promising new approach to the treatment of dyslipidemia. This article reviews the cholesterol metabolic pathways and the mechanism of action of the currently available lipid-modifying agents and introduces ezetimibe, the first selective cholesterol absorption inhibitor.