How the brain translates changes in body energy resources into appropriate changes in adaptive behaviour such as feeding and sleep is not well understood at the neural circuit level. We examined whether orexin/hypocretin neurons, which organize feeding and sleep in mammals, can sense glucose and other dietary nutrients. Glucose elicited electrical inhibition in hypocretin neurons, which was due to activation of K channels, and showed time-dependent adaptation in a subset of hypocretin cells. Glucose-sensing by hypocretin neurons did not require conventional metabolic machinery. Dietary amino-acids modulated the responses of hypocretin neurons to glucose, suggesting that hypocretin cell activity may depend on nutrient balance and thus couple meal composition to behaviour. Overall our results suggest that the brain may sense dietary composition through specialized nutrient-specific responses in subsets of behaviourally vital neurons.