Although a traditional goal of glycemic control in the treatment of diabetes mellitus is to normalize fasting plasma glucose, emerging data indicate that modulation of postprandial plasma glucose levels plays an important role in overall glycemic control. This article reviews the evidence linking postprandial glucose levels with long-term indices of diabetes control, such as glycosylated hemoglobin, lipid abnormalities, and the risk of microvascular and macrovascular complications. Early in the development of type 2 diabetes, the initial burst of insulin release in response to food intake is compromised, allowing postprandial hyperglycemia to develop. Meal-associated hyperglycemia further contributes to increase insulin resistance and decrease insulin production. Evidence of a strong correlation between high postprandial glycemic levels and the development of vascular complications underscores the significance of treating mealtime glycemia. Emerging drugs that reduce postprandial hyperglycemia include the D-phenylalanine derivative nateglinide, amylin derivative pramlintide, and glucagon-like insulinotropic peptide.