Even with optimal statin therapy, many patients with type 2 diabetes mellitus or metabolic syndrome fail to achieve all lipid targets and remain at high risk of cardiovascular events. Add-on lipid-modifying therapy that is effective in improving the triglyceride and high-density lipoprotein (HDL) cholesterol abnormalities characteristic of these conditions is a recommended approach to reduce this risk. Fibrates or niacin is a logical option, supported by clinical studies showing improved lipid control in combination with a statin. Of the fibrates, fenofibrate may offer microvascular benefits in type 2 diabetes—as demonstrated by the Diabetes Atherosclerosis Intervention Study (DAIS) and the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study—as well as a low risk of myopathy when combined with statins compared with gemfibrozil. Although there is good evidence that both agents favorably affect clinical outcome, we need to evaluate their impact against a baseline of statin therapy. We await data from ongoing large-scale studies to evaluate the efficacy and safety of these combinations and to determine the most appropriate option for reducing residual cardiovascular risk in this important patient population.