Fenofibrate is a PPAR-alpha agonist indicated for the treatment of hypertriglyceridemia and mixed dyslipidemia, and is approved for the treatment of hypercholesterolemia, lipid abnormalities commonly observed in patients at high risk of cardiovascular disease, including Type 2 diabetes and/or metabolic syndromes. Treatment with fenofibrate lowers triglycerides, raises HDL-cholesterol and decreases concentrations of small LDL-cholesterol particles and apolipoprotein B. Fenofibrate is particularly effective for reducing postprandial VLDL and LDL particle concentrations, and the increased oxidative stress and inflammatory response that occurs after a fatty meal. In addition, nonlipid pleiotropic effects mediated by PPAR-alpha are likely to contribute to the reduction in atherosclerosis progression and cardiovascular events, and have beneficial effects on diabetes-related microvascular diseases. While current approaches to treating dyslipidemia to prevent cardiovascular diseases focus on statin therapy, it is increasingly clear that substantial residual risk persists. The clinical significance of combination therapy with fenofibrate and a statin to macrovascular and microvascular risk is being evaluated in a large outcomes study.