AgRP= : Agouti-related protein; ARC= : arcuate nucleus; BDNF= : brain-derived neurotrophic factor; CART= : cocaine- and amphetamine-regulated transcript; CB1= : cannabinoid 1; CRH= : corticotrophin-releasing hormone; GABA= : γ-aminobutyric acid; MC4R= : melanocortin 4 receptor; MCH= : melanin-concentrating hormone; MSH= : melanocyte-stimulating hormone; NPY= : neuropeptide Y; POMC= : pro-opiomelanocortin; PVN= : paraventricular nucleus; TRH= : thyrotrophin-releasing hormone. The control of food intake and energy metabolism depends on the interaction among energy homeostasis, emotional factors (including the hedonic aspects of food), and environmental cues. These complex interactions involve a neural network distributed throughout the forebrain and brainstem and are mediated by multiple chemical signals. The hypothalamus is a nodal component of this network and contains several nuclei that exert a bidirectional homeostatic control on food intake and metabolism in response to peripheral signals that reflect the absorptive state and energy reserve. The insular cortex, orbitofrontal cortex, nucleus accumbens, amygdala, and dopaminergic ventral tegmental area neurons have a key role in control of feeding behavior in response to the reward or hedonic aspects of food. Over the past several years, there has been extensive research on the mechanisms controlling food intake and energy metabolism. Studies in experimental animals and functional neuroimaging studies in humans have provided insight into the complex interactions between the homeostatic and hedonic control of feeding behavior. These studies are relevant given the importance of obesity as a public health problem, and have identified several potential targets for treatment of this disorder. This experimental information also provides insight into the mechanisms underlying abnormal feeding behavior in neurologic disorders such as hypothalamic lesions and frontotemporal dementia. There are excellent reviews on homeostatic control of food intake and energy metabolism by the hypothalamus1–7 and the role of brain reward circuits in regulating feeding behavior.1,8–13 Only selected aspects will be emphasized here. The homeostatic control of food intake depends on long-loop mechanisms involving peripheral humoral and neural signals that are processed in the hypothalamus. Recent experimental studies2–7 have greatly refined the classic model of a “satiety” center, located in the ventromedial hypothalamus and a “feeding center,” located in the lateral hypothalamus, which was originally based on …