Over the past two decades, experimental studies following brain injury have shown that the central nervous system is dynamic and malleable to internal and external inputs. Neuromodulation and/or direct manipulation of motor and sensory experience can modify brain plasticity and functional outcome after experimental lesions. Specifically, pharmacologic modulation has been found to facilitate recovery of various behavioral deficits following occlusive injury. Additionally, the behavioral experience that induces long-term plasticity in motor and sensory maps after injury appears to be limited to those that entail the development of new skills. These data have strong application to human rehabilitation. This review will: (1) overview critical experimental studies that show that pharmacologic manipulation and/or specific behavioral experience may modify the functional organization of the injured brain and (2) review beginning studies which are exploring the application of this knowledge clinically.