Diabetes mellitus (DM) is defined as elevated blood glucose associated with absent or inadequate pancreatic insulin secretion with or without concurrent impairment of insulin. The cause of diabetes continues to be anonymity, although both genetics and environmental factors such as obesity and lack of exercise appear to play roles. Diabetes mellitus is a major and growing public health problem throughout the world, with an estimated worldwide prevalence in 2000 of 150 million people, expected to increase to 220 million people by 2010. Impaired insulin secretion, increased hepatic glucose production, and decreased peripheral glucose utilization are the core defects responsible for the development and progression of type 2 diabetes. However, the pathophysiology of this disease also includes adipocyte insulin resistance (increased lipolysis), reduced incretin secretion/sensitivity, increased glucagon secretion, enhanced renal glucose reabsorption, and brain insulin resistance/ neurotransmitter dysfunction. This chapter focuses on the treatment of hyperglycemia in patients with T2DM. The pathophysiology of type 2 DM has led to the introduction of new medications like dopamine agonist, amylin analogues, glucagon-like peptide 1 analogues, dipeptidyl peptidase-IV inhibitors, inhibitors of the sodium-glucose co-transporter 2, insulin-releasing glucokinase activators and glucagon receptor antagonists, metabolic inhibitors of hepatic glucose output and quick-release bromocriptine.