The past decade has witnessed dramatic advancements regarding the neuroendocrine control of food intake and energy homeostasis and the effects of peripheral metabolic signals on the brain. The development of molecular and genetic tools to visualize and selectively manipulate components of homeostatic systems, in combination with well-established neuroanatomical, electrophysiological, behavioral, and pharmacological techniques, are beginning to provide a clearer picture of the intricate circuits and mechanisms of these complex processes. In this review, we attempt to provide some highlights of these advancements and pinpoint some of the shortcomings of the current understanding of the brain's involvement in the regulation of daily energy homeostasis.