Lowering LDL cholesterol (LDL‐C) levels to reduce or prevent coronary artery disease (CAD) progression and cardiac events in hypercholesterolemic subjects is now widely accepted. The clinical benefit of lowering LDL‐C has recently been extended to individuals with normal or mildly elevated LDL‐C. Recent analyses of large primary and secondary CAD prevention trials, however, clearly demonstrated that reducing LDL‐C levels does not entirely account for the coronary event reduction associated with lipid‐lowering therapy. Growing and compelling evidence is emerging on the role of triglyceride‐rich lipoproteins (VLDL and IDL), high density lipoproteins (HDL), and small, dense LDL, as well as non lipid risk factors, in the regression or stabilization of atherosclerotic plaques of mild/moderate severity, which are associated with clinical cardiac events. Enzymes involved in the tight metabolic interrelationship between triglyceride‐rich lipoproteins, small, dense LDL and HDL levels may represent potential therapeutic targets for CAD prevention by favourably altering lipoprotein composition and physical properties in addition to the current therapeutic focus on lipoprotein levels. Curr Opin Lipidol 9:329–336. © 1998 Lippincott–Raven Publishers