Considerable evidence has demonstrated that use of statins has a beneficial impact on both progression of atherosclerosis and cardiovascular events. Accordingly, statins have been increasingly used in preventive strategies to reduce cardiovascular risk. More recent reports have demonstrated an incremental benefit with use of higher doses of statins and when used early in the setting of acute ischemic syndromes. Although lowering levels of low-density lipoprotein cholesterol is likely to underscore the majority of the clinical benefit, emerging evidence suggests that additional properties may also be important. In particular, a number of reports have demonstrated that modest elevations in levels of high-density lipoprotein cholesterol are likely to contribute to the benefit of statins. As a result, a favorable influence on the ratio of atherogenic and protective lipid species is likely to have the most profound impact on cardiovascular risk in statin-treated individuals.