Differences in LDL and HDL subclass distribution contribute to increased CAD risk through a variety of mechanisms. The inherited disorder characterized by an abundance of small, dense LDL particles increased CAD risk 3-fold and is associated with rapid arteriographic progression. The metabolic milieu associated with the small LDL trait includes insulin resistance, increased IDL, increased susceptibility to oxidative damage, impaired reverse cholesterol transport, and increased post prandial lipemia. Recent evidence indicates that the LDL IIIa+b region are the LDL subclass regions most associated with atherosclerosis. Improvement in LDL subclass distribution has been associated with arteriographic improvement significantly more than LDLC change. Therapeutic treatments including diet, and many pharmacologic interventions have a differential response in subjects characterized by an abundance of either small, or large LDL particles. Individual patient information regarding LDL and HDL subclass distribution can be used to improve medical management of the CAD patient that results in improved outcomes.