The neuropeptides, orexin A/ B, are produced in the lateral hypothalamic region of the brain and are widely released in the central nervous system including locomotor regions in the brainstem and the lumbar spinal cord. Multiple lines of evidence implicate orexin as being capable of influencing locomotion. However, the direct role of orexin in modulating locomotion is not known. Motor networks, which produce rhythmic patterns of activity for locomotion in the hindlimbs reside primarily in the lumbar spinal cord. My work addressed whether direct orexinergic modulation of spinal circuits can affect locomotor behavior. Data, obtained from neurogram recordings of isolated spinal cord preparations, show that application of orexin can powerfully affect the frequency of the locomotor rhythm. Additionally, experiments performed to delineate the effect of orexin onto isolated networks of the motoneurons showed a considerable increase in the firing rate of motoneurons, further suggesting orexin’s involvement in the locomotor circuitry.