Obesity is reaching endemic state and has a major impact on health and economy. In most cases obesity is caused by life style factors. However, the risk of becoming obese differs highly between people. Individual differences in life style, genetic, and neuroendocrine factors play a role in satiety, hunger and regulation of body weight. In a small percentage of children and adults with obesity, an underlying hormonal or genetic cause can be found. The aim of this review is to present and compare data on the extreme ends of the obesity and undernutrition spectrum in patients with Prader-Willi syndrome (PWS), Bardet-Biedl syndrome (BBS), acquired hypothalamic obesity in craniopharyngioma patients, and anorexia nervosa. This may give more insight in the role of neuroendocrine factors and might give direction for future research in conditions of severe obesity and underweight.