Pathogenesis of type 2 diabetes mellitus (T2DM) has led to newer treatments for the patients with this disease. Twenty-nine million individuals in the United States are reported to have T2DM, and an additional 79 million people have impaired glucose tolerance (IGT). This chapter covers the classification of diabetes mellitus, pathophysiology of type 2 diabetes mellitus, general approach to medical treatment of type 2 diabetes mellitus, profile of oral therapeutic agents, and philosophy of glucose control. Type 2 diabetes mellitus is a heterogeneous disorder with varying prevalence. Different ethnic groups show strikingly different risk. The pathobiology of disease is characterized by peripheral insulin resistance, impaired or unrestrained hepatic glucose output, and declining (eventually failing) pancreatic β-cell function. Normal glucose homeostasis involves two physiologic states of basal or postabsorptive state, and the absorptive or postprandial state.