Physical rehabilitation after spinal cord injury has been based on the premise that the nervous system is hard-wired and irreparable. Upon this assumption, clinicians have compensated for irremediable sensorimotor deficits using braces, assistive devices, and wheelchairs to achieve upright and seated mobility. Evidence from basic science, however, demonstrates that the central nervous system after injury is malleable and can learn, and this evidence has challenged our current assumptions. The evidence is especially compelling concerning locomotion. The purpose of this perspective article is to summarize the evidence supporting an impending paradigm shift from compensation for deficits to rehabilitation as an agent for walking recovery. A physiologically based approach for the rehabilitation of walking has developed, translating evidence for activity-dependent neuroplasticity after spinal cord injury and the neurobiological control of walking. Advanced by partnerships among neuroscientists, clinicians, and researchers, critical rehabilitation concepts are emerging for activity-based therapy to improve walking recovery, with promising clinical findings.