The brain receives information on the body's fuel supply through a bewildering array of chemical messengers that signal either negative or positive energy balance. Nesfatin-1, a secreted protein of previously unknown function, acts as a satiety factor. Nesfatin-1 suppresses appetite in both the short term and the long term, is made by neurons in brain centers that regulate energy balance and might act via melanocortin pathways. Nesfatin-1 is the latest addition to the surprisingly large number of chemical messengers telling the body that the tank is full.