Hypertriglyceridemia is now recognized as an independent risk factor of coronary artery disease (CAD). A recent secondary prevention study of CAD with a statin suggested that it may be prudent to target fasting triglycerides to less than 150 mg/dL. Secondary prevention trials of CAD with drugs acting primarily on triglycerides (fibrates) have shown that reducing triglycerides and increasing high-density lipoprotein (HDL) cholesterol, without significantly affecting low-density lipoprotein cholesterol slows down coronary artery luminal narrowing (Lopid Coronary Angiography Trial [LOCAT], Bezafibrate Coronary Atherosclerosis Intervention Trial [BECAIT], Bezafibrate Infarction Prevention [BIP]). Furthermore, Veterans Administration-HDL Intervention Trial (VA-HIT) and Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto-1 (GISSI) studies recently showed that gemfibrozil and fish oils, respectively, decreased CAD mortality in secondary prevention trials. Statins are also capable of significantly reducing high triglyceride levels. Further clinical studies are necessary to confirm in terms of mortality the beneficial effect of reducing triglycerides and increasing high-density lipoprotein cholesterol in secondary CAD prevention; whereas, in primary prevention the beneficial effect of drastically reducing triglycerides by the way of pharmacology needs to be proved.