Glucose homeostasis must be finely regulated. Changes in glucose levels elicit a complex neuroendocrine response that prevents or rapidly corrects hyper- or hypoglycemia. It is well established that different parts of the brain, particularly the hypothalamus and the brain stem, are important centres involved in the monitoring of glucose status and the regulation of feeding. The pioneering work of Mayer, including his proposal of the glucostatic theory, has recently received experimental support from the molecular, electro-physiological and physiological fields.Making the analogy with the beta cell of the islet of Langerhans, it has been proposed that glucose sensing could be assured in some cells of the brain by proteins such as glucose transporter 2, glucokinase and the ATP-dependent potassium channel. Furthermore, some pathological conditions such as diabetes and obesity have been shown to alter this glucose sensing system.These findings could lead to a better understanding of metabolic disorders, with hypoglycemia possibly being the most deleterious.