Hypothalamic obesity, or intractable weight gain after hypothalamic damage, is one of the most pernicious and agonizing late effects of CNS insult. Such patients gain weight even in response to caloric restriction, and attempts at lifestyle modification are useless to prevent or treat the obesity. The pathogenesis of this condition involves the inability to transduce afferent hormonal signals of adiposity, in effect mimicing a state of CNS starvation. Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis. Pharmacologic treatment is difficult, consisting of adrenergics to mimick sympathetic activity, or suppression of insulin secretion with octreotide, or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic gastric banding, vagotomy) have also been attempted with variable results. Early and intensive management is required to stave off the obesity and its consequences.