Brain plasticity refers to the capacity of the nervous system to change its structure and ultimately its function over a lifetime. There have been major advances in our understanding of the principles of brain plasticity and behavior in laboratory animals and humans. Over the past decade there have been advances in the application of these principles to brain-injured laboratory animals. To date, there have been few major applications of this knowledge to establish postinjury interventions in humans. A significant challenge for the next 20 years will be the translation of this work to improve the outcome from brain injury and disease in humans. The goal of this review is to synthesize the multidisciplinary laboratory work on brain plasticity and behavior in the injured brain to inform the development of rehabilitation programs. Learning outcomes: Readers will be able to: (a) identify principles of brain plasticity, (b) review the application of these principles to the treatment of brain-injured laboratory animals, and (c) consider the translation of the new treatments to brain-injured humans. (Contains 4 figures and 2 tables.)