Brain nutrient sensing permits fine regulation of physiological functions such as food intake and blood glucose regulation related to energy homeostasis. The mechanism of glucose sensing is the most extensively studied, and parallels have been drawn between pancreatic beta cells and neurons. Two types of glucose-sensing neuron have been identified, namely those whose activity is directly proportional to the glucose concentration, and those whose activity is inversely proportional to the glucose concentration. It was recently demonstrated that the mechanism depends on the amplitude of change in the glucose concentration. In some cases detection is probably not ensured by neurons themselves but by astrocytes, indicating that the two cell types are coupled in some way. Glucose sensing can be modulated by other nutrients (particularly fatty acids) and also by hormones (insulin, leptin and ghrelin) and peptides (NPY). The subtle cellular and molecular mechanisms involved in glucose sensing probably explain reported discrepancies in the expression of glucose transporters, hexokinases and channels. Astrocytes might also be involved in one type of response, thus adding a new level of complexity.