The brain or central nervous system (CNS) utilizes a vast amount of energy to sustain its basic functions, and most of the energy in the brain is derived from glucose. Whole-body energy and glucose homeostasis in the periphery of the human body are regulated by insulin, while the brain had been considered as an “insulin-insensitive” organ, because bulk brain glucose uptake is not affected by insulin in either rodents and humans. However, recently it has become clear that the actions of insulin are more widespread in the CNS and are a critical part of normal development, food intake, and energy balance, as well as plasticity throughout adulthood. Moreover, there are substantial evidence demonstrating that brain insulin is derived from pancreas, neurons, and astrocytes. In this chapter, I reviewed recent progress in roles of insulin in the brain, expression of insulin genes, and multiple origins of the brain insulin.