Orexin neurons have been suggested to stimulate eating; however, loss of these cells in mice leads to obesity. Here, the authors used fibre photometry to measure calcium signalling in orexin neurons in freely behaving fasted and fed mice and found that the activity of these cells decreased quickly after eating onset and remained low during the period of feeding. Moreover, conditional inactivation of orexin neurons in adult mice led to an overeating phenotype. Thus, these data suggest an inhibitory relationship between these neurons and eating.