Obesity is a common sequel to tumours of the hypothalamic region and their treatment with surgery and radiotherapy. The prevalence of hypothalamic obesity has been underestimated because it may take some years to develop, and the problem has been under-recognized by physicians. Weight gain results from damage to the ventromedial hypothalamus which leads, variously, to hyperphagia, a low metabolic rate, autonomic imbalance, growth hormone (GH) deficiency and various other problems that contribute to weight gain. However, with the exception of GH replacement, few clinical trials have evaluated significant numbers of patients and so the roles of various behavioural, dietary, pharmacological and obesity surgery approaches are controversial. Sufficient knowledge exists to identify those at high risk of hypothalamic obesity so that weight gain prevention approaches can be offered. In those who are already obese, we propose that the principal causal mechanisms in individual patients should be considered as a basis for guiding clinical management.