Hypocretin/orexin neurons of the hypothalamus are essential for normal wakefulness, feeding behaviour, and reward seeking. Their electrical activity is directly silenced by glucose, providing a potentially important link between energy state and behavioural coordination. However, the cellular mechanisms underlying this electrical silencing are not well understood. Our new experiments show that the orexin/hypocretin glucosensors display a novel sugar selectivity, detecting mannose, D-glucose, and 2-deoxyglucose, but not galactose, L-glucose, fructose or alpha-methyl-D-glucoside. Furthermore, conventional glucose metabolism does not appear critical for orexin cell glucosensing: the effects of extracellular glucose on orexin cells are not mimicked by intracellular glucose or lactate, and are not affected by glucokinase inhibitors. We also show that orexin cell glucosensing also exhibits an unusual temporal profile. About 70% of orexin neurons are inhibited by glucose only transiently, self-restoring their firing despite high sugar levels. The remaining 30% of cells display sustained inhibition that follows the time-course of glucose application. The transient and sustained glucosensor cells display significant differences in their ion channel expression. The implications of these findings for the control of feeding and cognitive arousal will be discussed.