Type 2 diabetes mellitus is a common, chronic disease affecting nearly 6% of the adult US population. It remains a leading cause of morbidity and mortality in Wisconsin as well as the country. Multiple lines of evidence show that controlling blood glucose in patients with type 2 diabetes can significantly decrease the development of and/or progression of microvascular complications as well as the macrovascular complications of diabetes. There are now four different classes of oral medications which are available to treat diabetes-sulfonylureas, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors. Each class works differently to treat the underlying defects of diabetes which include impaired insulin secretion, insulin resistance and exaggerated postprandial hyperglycemia. This article will compare and contrast the different agents available, including appropriate use of each agent as monotherapy and in combination therapy. It will also discuss use of insulin in the patient who has failed oral therapy. Rational use of these tools, tailored for the individuals metabolic abnormalities, should allow for good glycemic control in the majority of patients with type 2 diabetes mellitus. Relaxation, massage, opium, and moderate exercise were among the recommended options for treatment of diabetes mellitus nearly 100 years ago. In the late nineteenth century, diabetes was a poorly characterized disorder, which was increasing in prevalence even at that time. Today, the underlying defects contributing to the development of type 2 diabetes are better understood, and include peripheral insulin resistance, relative pancreatic beta-cell insufficiency, increased hepatic glucose output, and an exaggerated postprandial glucose excursion. However, despite our better understanding of the disease, the prevalence of type 2 diabetes continues to increase in the US, now afflicting over 6% of the population. As our population ages and the proportion of obese people increases, we can expect to see a marked increase in the prevalence of diabetes in the future. Fortunately, our treatment options for type 2 diabetes have expanded remarkably within the last few years. Along with these new treatment options comes the exciting, although likely expensive, possibility of prevention of type 2 diabetes in at risk individuals.