Increasing evidence suggests that the quality-rather than just the quantity-of low-density lipoproteins (LDLs) exerts a great influence on cardiovascular risk. LDLs comprise multiple subclasses with discrete size and density, and different physicochemical composition, metabolic behaviors, and atherogenicity. Individuals generally cluster into 2 broad subgroups. Most have a predominance of large LDLs, and some have a higher proportion of small particles. Small, dense LDLs are good predictors of cardiovascular events and progression of coronary artery disease. Their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Several studies have shown that therapeutic modulation of LDL size and subclass is of great benefit in reducing the risk of cardiovascular events. This seems particularly true for statins and fibrates when they are administered to higher-risk patients, such as those with type 2 diabetes or vascular disease. Data reporting outcomes with the use of rosuvastatin, the latest statin molecule introduced to the market, and ezetimibe, a cholesterol absorption inhibitor, are promising.