Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that arises from lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. PWS has been classically described as having two nutritional phases, but detailed descriptions recently led to the characterization of four main nutritional phases, with a particular emphasis on the fact that excessive weight gain occurs prior to hyperphagia. Patients with PWS show reduced satiety and early return of hunger. They are prone to eating nonfood items (pica) or contaminated foods, and to combine foods inappropriately. The abnormal feeding behavior in PWS includes a morbid obsession with food, food stealing, hoarding, and foraging. Evaluation of eating behavior has not yet been standardized in PWS, but questionnaires are being validated and this will enable caregivers to better characterize certain features of the syndrome, such as satiety and hyperphagic behavior, drive, and severity. PWS has been described as a genetic hypothalamic syndrome, because it includes hyperphagia as well as temperature dysregulation, sleep-wake cycles abnormalities, and metabolic and endocrine disorders. Recent data also suggest more complex dysfunctions involving the corticolimbic areas. In any case, the most striking and specific defects in PWS feeding and satiety signals is the high circulating level of the orexigenic stomach-derived hormone ghrelin and the decreased level of pancreatic polypeptide. Hypergrhelinemia could explain the obesity and the GH deficiency. Interestingly, these two main abnormal signals may explain the major feeding disturbances described in individuals with PWS. Part of their action requires an intact vagal nerve reflex and they both regulate gastric emptying. These findings suggest that the eating behavior of people with PWS may be due to decreased satiety rather than to increased hunger. Recent functional MRI findings suggest that hyperphagia may be linked to at least two mechanisms involving limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and regions that regulate food intake (e.g., the medial PFC). Management of PWS involves strict and permanent environmental control with early institution of a low-calorie, well-balanced diet, with regular exercise, rigorous supervision, restriction of access to food and money, with consideration of legal and ethical obligations, and appropriate psychological and behavioral counseling for the patient and family. The effects of GH treatment on hyperphagia remain to be demonstrated, but GH prevents the increase in BMI and the decrease in lean-body mass observed in patients without treatment.