Research on the role of peripheral organs in the regulation of glucose homeostasis has led to the development of various monotherapies that aim to improve glucose uptake and insulin action in these organs for the treatment of type 2 diabetes. It is now clear that the central nervous system (CNS) also plays an important part in orchestrating appropriate glucose metabolism, with accumulating evidence linking dysregulated CNS circuits to the failure of normal glucoregulatory mechanisms. There is evidence that there is substantial overlap between the CNS circuits that regulate energy balance and those that regulate glucose levels, suggesting that their dysregulation could link obesity and diabetes. These findings present new targets for therapies that may be capable of both inducing weight loss and improving glucose regulation.