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It is clear that the brain plays a key role in the maintenance of glucose homeostasis. The exact mechanism(s) by which this occurs remains a mystery. However, glucose sensing neurons stand out as prime candidates which enable the brain to sense and respond to changing glucose levels. These neurons are located in key brain regions involved in the regulation of glucose and energy homeostasis. They are also located in the periphery. Glucose sensing neurons are exquisitely sensitive to small changes in extracellular glucose within the physiological range. Their glucose sensitivity becomes impaired under conditions where central glucose sensing mechanisms become dysfunctional. This review discusses the locations of central and peripheral glucose sensing neurons and the mechanisms by which they sense glucose. Putative physiological roles of both central and peripheral glucose sensors are described. Finally, the relationship between glucose and other nutrient signals to the brain is discussed. [ABSTRACT FROM AUTHOR] more...