The incretins have emerged as key targets in the modern treatment of type 2 diabetes mellitus. Understanding the physiology of the incretins is essential to the physician's ability to appropriately use emerging pharmacotherapies that target this system. This review describes incretin physiology and discusses recent trials of drugs that modulate this system in the treatment of type 2 diabetes. A MEDLINE search Using the terms "GLP-1" (ie, glucagon-like peptide 1) "incretins," "exenatide," and "DPP-IV inhibitors" (ie, dipeptidyl pedtidase IV inhibitors) was performed, and pertinent articles from the past 10 years were reviewed. Articles describing incretin physiology and clinical trials with exanatide and dipeptidyl peptidase IV inhibitors were identified and discussed. As the articles show. new medications manipulating, the incretin system are in important part of treating type 2 diabetes. The cost of these drugs and their potential side effects in comparison with existing agents must be considered when they are being selected as part of a treatment regimen. However, the evidence to (Lite offers much promise and enthusiasm. Mt Sinai J Med 76:244-256, 2009. (C) 2009 Mount Sinai School of Medicine