The neural sensing of nutrients during food digestion plays a key role in the regulation of hunger. Recent data have emphasized that the extrinsic gastrointestinal nervous system is preponderant in this phenomenon and in its translation to the control of food intake by the central nervous system (CNS). Nutrient sensing by the extrinsic gastrointestinal nervous system may account for the satiation induced by food lipids, the satiety initiated by food protein, and for the rapid benefits of gastric bypass surgeries on both glucose and energy homeostasis. Thus, this recent knowledge provides novel examples of the mechanisms that control food intake and body weight, and this might pave the way for future approaches to the prevention and/or treatment of obesity.