Given the demonstrated importance of the incretin effect on the prandial insulin response, augmentation of the incretin effect in people with type 2 diabetes is an important pharmacological approach to glycemic management. In recent years, the use of incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, has increased dramatically due to their demonstrated efficacy, low risk of hypoglycemia when used as monotherapy, and reasonable tolerability. Given their effects on glycemic parameters and the likelihood of aiding in weight loss, GLP-1 receptor agonists provide a unique treatment option for people with type 2 diabetes. Increased clinical experience and study of incretin-based therapies will help answer questions about safety issues that have arisen from post-marketing reports. The potential benefit of incretin-based therapies in the treatment of people with type 2 diabetes and cardiovascular disease is currently an active area of inquiry. While the potential benefits of incretin-based therapies in the arena of cardiovascular risk reduction are promising, results from ongoing outcomes-based studies will help determine the role of these agents in this setting.