Reduced levels of high-density lipoprotein (HDL) cholesterol represent an important risk factor for the development and progression of coronary artery disease. In recent years, clinical outcome studies have verified that statin therapy may reduce the risk of initial or recurrent cardiovascular events in subjects with elevated or "normal" cholesterol levels. Subgroup analysis has also revealed that patients with low HDL benefit from this therapy. Two recently presented outcome trials using fibrate therapy also demonstrated a potential role for these medications in subjects with low HDL. The use of various HDL raising agents, singly or in combination on arteriographic progression and their potential mechanisms of action are reviewed. The latter may be an important consideration in the treatment of high-risk patients with low HDL.