The present article reviews the efficacy of fenofibrate in combination with routinely used lipid-lowering drugs, some oral antidiabetic agents and other drugs in improving lipid profile and reducing cardiovascular risk. Because of its ability to reduce triglyceride (TG) levels and increase high-density lipoprotein-cholesterol (HDL-c), fenofibrate is an effective complementary agent to cholesterol-lowering drugs in the treatment of patients with mixed dyslipidemia or low HDL-c levels. Thus, the addition of fenofi brate to statin therapy produces a complementary reduction in TG of 7%-34%, an additional increase in HCL-c of 2%-20%, a reduction in non-HCL-c of 6%-8% and an increase in the proportion of large/small LDL particle subspecies in comparison with statin therapy alone. In the subgroup of patients in the ACCORD study with TG >= 204 mg/dL and HDL-c <= 34 mg/dL, fenofibrate contributed to the reduction in cardiovascular risk. These results have been corroborated by two recent meta-analyses of the main studies with fibrates. The combination of fenofibrate and ezetimibe produced greater reductions in non-HDL-c, apoB and C-reactive protein than that produced by either of these two drugs alone. The addition of omega-3 fatty acids to fenofibrate significantly reduced TG levels by 17.5%-28%. The combination of fenofibrate and metformin allowed TG and HDL-c to return to normal levels in 50% and 35%, respectively. Fenofibrate also reduces hypertriglyceridemia if combined with pioglitazone. (C) 2012 Sociedad Espanola de Arteriosclerosis. Published by Elsevier Espana, S.L. All rights reserved.