Constraint-Induced Movement therapy or CI therapy is an approach to physical rehabilitation elaborated from basic neuroscience and behavioral research with primates. The application of the CI therapy protocol to humans began with the upper extremity after stroke and was then modified and extended to cerebral palsy in young children, traumatic brain injury, and multiple sclerosis. A form of CI therapy was developed for the lower extremities and has been used effectively after stroke, spinal cord injury, fractured hip, multiple sclerosis, and cerebral palsy. Adaptations of the CI therapy paradigm have also been developed for aphasia, focal hand dystonia in musicians, and phantom limb pain. Human and animal studies using a variety of methods provide evidence that CI therapy produces marked neuroplastic changes in the structure and function of the CNS. Moreover, these changes appear to be important for the intervention's therapeutic effect. © 2013 Elsevier B.V.