Long direct bulbospinal projections are known to convey descending activation of locomotor networks. Less is understood about the role, if any, of propriospinal mechanisms in this function. Here we review our recent studies on propriospinal neurons in the in vitro neonatal rat brainstem-spinal cord preparation. Neurochemical suppression of synaptic activity in the cervicothoracic spinal cord blocked locomotor-like activity, suggesting synaptic relays make a critical contribution to descending transmission of the locomotor signal. Staggered contralateral hemisections in the cervicothoracic region, intended to eliminate all long direct bulbospinal transmission, failed to suppress locomotion, suggesting the propriospinal system alone is sufficient. Midsagittal lesion experiments showed that locomotor-related commissural components are required for rhythm generation in response to electrical stimulation of the brainstem and are redundantly distributed. No single segment was essential, although a bi-directional gradient was noted, centered on the thoracolumbar junction. These results strongly favor a role for propriospinal mechanisms in the activation of locomotion and suggest that propriospinal neurons are a logical target for interventions to restore locomotor function after spinal cord injury.