Constraint-Induced Movement Therapy (CI therapy) refers to a family of treatments for motor disability that combines constraint of movement, massed practice, and shaping of behavior to improve the amount of use of the targeted limb. CI therapy has controlled evidence for efficacy that supports its benefit for patients with chronic disability following central nervous system injury, regardless of their age or the interval since illness onset. Furthermore, the benefits transfer to real-world measures of limb use. Significant functional improvement may occur even after the patient has been treated with conventional physical therapy. In this paper we review the evidence for the efficacy of CI therapy, particularly for chronic stroke hemiparesis, but also for diverse other chronic disabling illnesses, including non-motor disorders such as phantom limb pain and aphasia. The adaptation of the therapy to the stroke clinic is described, along with a review of the neurophysiologic mechanisms that are postulated to underlie the treatment benefit (overcoming learned nonuse, plastic brain reorganization). Critical to the success of CI therapy is its modification according to disease factors, economic considerations, limitations of the practice setting, and the cognitive and physical status of the patient. We conclude by recommending future areas for research on CI therapy.