Dipeptidyl peptidase-4 inhibitors (DPP-4s), also commonly called gliptins, are a relatively new class of drugs for the treatment of type 2 diabetes. These agents work in a unique way to improve insulin secretion from the Beta-cells of the pancreas in response to an increase in blood sugar and simultaneously decrease glucagon output from the a-cells of the pancreas, which results in decreased hepatic glucose output. Specifi cally, gliptins decrease the breakdown of glucagon-like peptide-1 (GLP-1) such that the circulating levels reach the high normal physiologic GLP-1 range. This results in more prompt and appropriate secretion of insulin and suppression of glucagon in response to a carbohydrate-containing meal or snack. The change in glucagon correlates linearly with improvement in glucose tolerance. Since these drugs improve insulin secretion in response to an increase in blood glucose, it seems appropriate to pair them with drugs that have a different mechanism of action, such as insulin sensitizers or metformin. In fact, improvements in fasting and postprandial glucose levels, improved beta-cell function, and improvement in HbA1c levels have been demonstrated in numerous clinical trials using different gliptins as monotherapy and in combination with various type 2 diabetes medications, including insulin. This article reviews data from a number of clinical trials, presentations, and abstracts indicating the importance of the DPP-4 inhibitors sitagliptin, vildagliptin, and alogliptin both alone and in combination with insulin sensitizers in the treatment of type 2 diabetes.