Despite the interruption in communication between the brain and lower centers by spinal cord injury, many of the neurons engaged in generating locomotion survive. Several strategies have been used to activate spinal cord circuitry independent of the higher centers, including direct electrical stimulation, pharmacological agents, and training programs that involve moving the legs through the motions of walking. Ambulatory leg movements are achieved by these interventions, leading to substantial functional improvements in the subset of patients with incomplete spinal cord injury. The neurobiological basis for these phenomena likely involves activity-dependent reconfiguration of synaptic connections within the spinal cord. Fostering this process may lead to further benefits for individuals with spinal cord injury.