Whether low-fat, high-carbohydrate (CHO) diets or moderately high-fat, high-monounsaturated fatty acid (MUFA) diets are preferable for the treatment and prevention of diabetes has been a matter of debate. High-fat diets based on MUFA-rich oils or whole foods have been compared with high-CHO diets for effects on several cardiovascular risk outcomes in diabetic subjects. Early studies using metabolic diets with wide differences in total fat content (15-25% of energy) generally found a beneficial effect of MUFA diets on glycemic control and serum lipids. Recent studies using prescribed diets with a difference of </= 15% of energy in total fat between low-fat and high-MUFA diets show similar effects on glycemic profiles but still favor MUFA diets for effects on triacylglycerols and HDL cholesterol. It is unclear whether postprandial fat clearance is impaired by CHO diets and improved by MUFA diets, independent of effects on fasting triacylglycerol concentrations. Unless one diet contains abundant antioxidants, the 2 dietary approaches appear to have similar effects on LDL oxidation. Low-fat diets, however, are associated with atherogenic, dense LDL particles, while normal, buoyant LDL predominate with high-fat diets irrespective of fatty acid composition. Limited experimental evidence suggests that MUFA diets favorably influence blood pressure, coagulation, endothelial activation, inflammation, and thermogenic capacity. Energy-controlled high-MUFA diets do not promote weight gain and are more acceptable than low-fat diets for weight loss in obese subjects. Thus, there is good scientific support for MUFA diets as an alternative to low-fat diets for medical nutrition therapy in diabetes.