In recent years the brain has been identified as a major insulin-sensitive organ. In humans insulin from the periphery can reach the brain and regulate its activity. Important insulin-sensitive brain areas include the hypothalamus, fusiform gyrus and prefrontal cortex. Brain insulin action regulates important physiological functions in humans, such as food intake, body weight regulation, whole body glucose and energy metabolism and cognition. In obese persons central nervous insulin resistance has been identified and important insulin effects are therefore diminished. Further research could reveal entirely new approaches for successful prevention and treatment of obesity, diabetes and neurodegenerative diseases.