Internally and externally triggered movement is crucial for survival and is controlled by multiple interconnected neuronal populations spanning many brain areas. Lateral hypothalamic orexin/hypocretin neurons are thought to play a slow, modulatory part in this scheme through their key role in promoting metabolism and wakefulness. However, it is unknown whether orexin/hypocretin neurons participate in rapid neural processing, leading to immediate movement. Furthermore, their role in sensorimotor transformations remains unknown. Here we use cellular-resolution Ca 2+ imaging and optogenetics to show that orexin/hypocretin cells are instantaneous regulators of self-generated and sensory-evoked movement. They are activated before and during movement, preventing this activation reduces self-generated locomotion, and optogenetic mimicry of this transient activation rapidly initiates locomotion. We find that the same orexin neurons whose activity predicts movement initiation are rapidly controllable by external sensory stimuli, and silencing orexin cells during sensation prevents normal motor performance. These findings place orexin neurons in a physiological position of unexpectedly rapid and strong sensorimotor control. * -( Figure 3E), where S is spike output, F is light pulse frequency, P is movement probability, EC50 is half-maximal response and IC50 half-maximal decrease. Fitting was done using custom routines in Matlab.