Macrovascular complications of diabetes are the leading cause of morbidity and mortality in patients with diabetes and may begin well before diabetes is diagnosed. The precise mechanism of how postprandial hyperglycemia contributes to the pathogenesis of cardiovascular disease is not fully known but may be a result of direct effects on the vasculature. Several epidemiologic studies have suggested that increased glycemic exposure, especially postchallenge or postprandial hyperglycemia, is an independent risk factor for macrovascular disease with no apparent upper or lower threshold. Evidence is emerging that this association is also present in the prediabetic and nondiabetic states. In fact, therapies targeting postprandial hyperglycemia have shown reductions in cardiovascular events in patients with impaired glucose tolerance. Meal-related self-monitoring of blood glucose can inform patients and their healthcare providers about postprandial glycemic excursions so that diet, exercise, or medications can be adjusted.