Before 1950, there was no clear perception of the interrelationship of serum lipids, atherosclerosis, and coronary heart disease. Since then, research laboratories have made conflicting claims for the most useful measurement of the serum lipid levels in detecting and managing coronary heart disease. Emphasis has been placed in turn on the measurement of levels of serum cholesterol, lipoproteins, triglycerides, and, currently, cholesterol and lipoproteins again. Physical separation and characterization of serum lipoproteins by ultracentrifugation and electrophoresis resulted in two classification systems for lipoproteins based on hydrated density and electrophoretic mobility, respectively. Two operational by-products were the atherogenic index, an empirical formula supposed to correlate with coronary heart disease, and a phenotype system for classification of the lipoproteinemias. Current National Heart, Lung, and Blood Institute criteria for atherosclerosis risk implicate elevated levels of cholesterol and low-density lipoprotein cholesterol, and decreased levels of high-density lipoprotein cholesterol. Although triglycerides are closely associated with cholesterol in lipoprotein molecules and are positively associated with cardiovascular disease, there is no strong evidence of elevated levels of plasma triglycerides as an independent risk factor in coronary heart disease. Elevated levels of triglycerides can help identify persons with increased risk of cardiovascular disease from other causes, but screening for hypertriglyceridemia is not recommended. Apolipoproteins and lipoprotein Lp(a) are briefly discussed.