Emerging evidence suggests that subclasses of LDL, characterized by variations in density, size, and chemical composition of LDL particles, are of important clinical significance. Accumulating case-control studies demonstrate that a predominance of small, dense LDL particles (LDL subclass phenotype B) is associated with an increased risk of coronary heart disease, and several potential atherogenic mechanisms have been proposed. New studies also demonstrate that LDL subclass phenotype B is an integral feature of the insulin resistance syndrome. In addition to the well-documented genetic influences on LDL subclass distributions, lipid-altering drugs, diet, and exercise all appear to affect LDL subclasses. A better understanding of this combination of genetic and environmental influences could lead to the development of effective intervention strategies for the prevention of coronary heart disease.