Over the past 15 years, our understanding of how the nervous system responds to brain injury, spinal cord injury, and stroke has expanded exponentially. Research demonstrates that the CNS, once thought to be unable to regenerate, maintains a degree of plasticity that responds to activity and pharmacologic therapy, producing both neurophysiologic changes and clinical recovery. Removing barriers to optimize axonal regrowth appears to further enhance this plasticity. Functional imaging, magnetic stimulation, and quantitative electroencephalography allow investigators to localize and monitor changes in brain activity during both spontaneous recovery and treatment paradigms. Neurorehabilitation research is difficult and funding is insufficient. Newer research approaches and better collaboration between researchers and clinicians are warranted. Clinical adoption is slow because of cost and time pressures. Demonstration that treatments promoting CNS plasticity result in better functional outcomes and reduced overall costs is needed.