Paralysis following spinal cord injury (SCI) continues to be an intractable problem. Here, the authors studied SCI in rats that induced complete hindlimb paralysis but left a small 'bridge' of undamaged tissue. A combination of electrical stimulation and monoaminergic agonists was applied to spinal circuits downstream of the lesion. The rats were then placed in a supportive robotic postural interface that allowed bipedal locomotion and presented with a food reward that was just out of reach. Within 6 weeks of training, rats with neurochemical prostheses were able voluntarily to initiate locomotion towards the food. This supports previous studies that suggest that active training, combined with motivational sensory cues, has potential as a rehabilitation approach in humans with paralysing SCI.