Type 2 diabetes is a progressive disease. The glucose control of persons with type 2 diabetes usually worsens over time. As seen in the UKPDS patients on one oral medication often fail. Treatment of this chronic, progressive disease usually requires multiple medications often in combination with insulin. However, despite the availability of many medications, the majority of people with type 2 diabetes are unable to maintain long-term glycemic control. The high prevalence of obesity compounds this problem as it may worsen hyperglycemia and insulin resistance. Ineffective implementation of existing pharmacotherapy is a significant factor contributing to suboptimal care. The efficacy of available therapies diminishes as the disease progresses because of a steady decline in pancreatic beta cell function. Innovative approaches to treatment are required and new agents are constantly being sought. Recent research has provided new insight to the role of alpha cells, glucagon and incretin hormones in the pathogenesis of type 2 diabetes. Recently several compounds became available for treatment. This is a review of incretin mimetics and enhancers and their clinical utility.