Hepatic lipase catalyses the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Genetic deficiency of this enzyme is associated with a unique plasma lipoprotein profile, characterized by hypertriglyceridemia and elevated concentrations of intermediate density lipoproteins and HDL. Recent studies have identified common polymorphisms in the hepatic lipase gene that are associated with low hepatic lipase activity and increased concentrations of large HDL. Association studies using these polymorphisms are elucidating the effects of variation in hepatic lipase activity on plasma lipoprotein concentrations and susceptibility to coronary atherosclerosis.