The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that the benefit of optimal glucose control in type 2 diabetes is a significant reduction in diabetes-related complications. In addition, the UKPDS also demonstrated that type 2 diabetes is a progressive disorder. Whereas many patients may initially receive good glucose control from a single medication, they are likely to require multiple medications to maintain this same level of glucose control as the disease progresses. The recent introduction of several new classes of glucose-lowering medications has allowed health care providers to explore the use of these medications alone and in combination to help patients with type 2 diabetes maintain optimal glucose control. Therefore, it is important to understand the physiologic actions, benefits, and risks of these medications in the treatment of type 2 diabetes.