The importance of maintaining effective glycemic control in patients with type 2 diabetes mellitus (T2DM) is well known. It is increasingly recognized that postprandial hyperglycemia is an important component of the overall glycemic burden, though there is as yet a paucity of data showing that lowering of postprandial plasma glucose (PPG) reduces risk of T2DM complications. The contribution of PPG to overall glycemic control is greatest when glycated hemoglobin (HbA1c) is approximately 7% to 8%. Clinical studies show that targeting PPG can improve glycemic control and long-term prognosis in patients with T2DM. Guidelines for T2DM management now include target levels for PPG as treatment goals. One effective approach to PPG control is achieved using mealtime administration of insulin with a rapid onset of effect and a short duration of action, so that PPG excursions are limited without increased risk of hypoglycemia. Basal-bolus and biphasic insulin regimens achieve good PPG control, even in patients unable to reach glycemic targets with other treatments. Although clinical studies are increasingly including PPG as an endpoint, more interventional studies are needed to investigate the effect of different treatment regimens on PPG and the effect of PPG on clinical outcome. This will facilitate future recommendations for the most effective treatment of T2DM. Postprandial glucose is an important glycemic burden in many patients; routine targeting and regular monitoring has potential to ameliorate the cardiovascular complications of T2DM.