High-density lipoprotein (HDL), the most abundant human plasma lipoprotein, plays a major role in reverse cholesterol transport, which recycles cholesterol from peripheral cells to the liver. HDL constitutes a heterogeneous group of particles differing in density, size, electrophoretic mobility, and apolipoprotein content. HDL can therefore be fractionated into discrete subclasses by different techniques according to their physicochemical properties. The clinical significance of HDL differs with the subclasses, especially with respect to coronary heart disease, alcohol intake, longevity, dyslipoproteinemia, dietary fat content, and hypolipidemic drugs. Because of their structural and functional diversity, HDL subclasses generate considerable hope that they may help to improve the identification of individuals at an increased risk of developing coronary heart disease.