The prevalence of type 2 diabetes mellitus (DM) is increasing substantially in the United States. Almost 24 million people have the disease, with most of these patients treated by primary care physicians. Optimal treatment of type 2 DM requires physicians to understand the pathophysiology of this disorder. Once the physiologic defects are determined, lifestyle interventions and glucoselowering medications can be prescribed to minimize the state of chronic hyperglycemia and to address the pathophysiologic defects associated with type 2 DM. Other metabolic abnormalities, including hyperlipidemia, hypertension, and oxidative stress, must also be addressed to reduce the patient's risk of cardiovascular disease. The incretin system plays a role in the pathogenesis of type 2 DM. Incretin-based therapies, including glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors, have shown efficacy and safety in treating type 2 DM and have been reviewed in consensus treatment algorithms. This article provides an overview of the role of incretin-based therapies in the management of patients with type 2 DM and how primary care physicians can incorporate these agents into their practice.