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Current treatment for atherosclerotic heart disease consists mainly of the administration of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or 'statin' class of drugs. Statins, which lower low-density lipoprotein cholesterol levels and have numerous other effects in the arterial wall, have shown remarkable efficacy and an exemplary safety profile in preventing both primary and secondary atherosclerotic events. These agents, however, are less effective at raising high-density lipoprotein, lowering triglycerides and decreasing insulin resistance--all of which are important targets for the prevention of ischemic vascular disease. Agonists of the peroxisome proliferator-activated receptors (PPARs) are among the most promising drug candidates to target these treatment gaps. Only PPARalpha agonists have been shown clinically to improve the outcome of atherosclerotic heart disease; however, it will only be a matter of time before we know whether compounds that modulate the function of PPARgamma and beta/delta are also efficacious at combating atherosclerosis.