New approaches to lipid lowering include new uses of proven treatments and development of novel agents. Several large-scale clinical trials are assessing whether additional reduction of low-density lipoprotein cholesterol (LDL-C) levels with statin therapy results in additional benefit in coronary artery disease prevention. Statins with increased LDL-C-lowering potency, such as the new statin rosuvastatin (formerly known as ZD4522), have been developed and are in advanced-phase clinical trials. New cholesterol transport inhibitors, such as ezetimibe, have been found to produce significant reductions in intestinal cholesterol absorption, and new bile acid transport inhibitors are in development. Inhibitors of acyl coenzyme A:cholesterol acyltransferase, which can reduce cholesterol storage in macrophages and thereby in arterial lesions, have also been developed, with the agent avasimibe currently being evaluated in phase 2/3 trials. Combination approaches hold considerable promise, including combined use of statins with fibrates, niacin, and the new sterol absorption inhibitors.