In 1995, we described a new model for adiposity regulation. Since then, data regarding the biology of body weight regulation has accumulated at a remarkable rate and has both modified and strengthened our understanding of this homeostatic system. In this review we integrate new information into a revised model for further understanding this important regulatory process. Our model of energy homeostasis proposes that long-term adiposity-related signals such as insulin and leptin influence the neuronal activity of central effector pathways that serve as controllers of energy balance.