Insulin resistance is a hallmark feature of type 2 diabetes and obesity. In addition to the classical view that insulin resistance in the liver, muscle, and fat disrupt glucose homeostasis, studies in the past decade have illustrated that insulin resistance in the hypothalamus disregulates hepatic glucose production and food intake, leading to type 2 diabetes and obesity. My lecture argues that insulin signaling in the dorsal vagal complex regulates hepatic glucose production and food intake. A thorough understanding of the physiological and pathophysiological mechanisms of insulin action in the hypothalamus and dorsal vagal complex is necessary for identifying therapeutic targets for obesity and type 2 diabetes.