It is well established that strict glycemic control (hemoglobin A1c <7.0%) can prevent the microvascular complications of diabetes mellitus. Recent studies indicate that elevated plasma glucose concentrations are an independent and clinically significant risk factor for cardiovascular disease in nondiabetic and diabetic individuals. Thus, isolated postprandial hyperglycemia (2-hour postprandial glucose level >140 mg/dL [>7.8 mmol/L]) in the face of normal fasting plasma glucose (<110 mg/dL [<6.1 mmol/L]) and normal hemoglobin A1c (<6.1%) values is associated with a 2-fold increased risk of death from cardiovascular disease. These observations imply that more strict glycemic control is required to prevent macrovascular disease than microvascular disease. This review summarizes epidemiologic and experimental studies linking postprandial hyperglycemia to cardiovascular disease and therapeutic approaches available and in development to treat this disorder.