Over the past 20 years, evidence has mounted regarding the capacity of the central nervous system to alter its structure and function throughout life. Injury to the central nervous system appears to be a particularly potent trigger for plastic mechanisms to be elicited. Following focal injury, widespread neurophysiological and neuroanatomical changes occur both in the peri-infarct region, as well as throughout the ipsi- and contralesional cortex, in a complex, time-dependent cascade. Since such post-injury plasticity can be both adaptive or maladaptive, current research is directed at understanding how plasticity may be modulated to develop more effective therapeutic interventions for neurological disorders, such as stroke. Behavioral training appears to be a significant contributor to adaptive plasticity after injury, providing a neuroscientific foundation for the development of physical therapeutic approaches. Adjuvant therapies, such as pharmacological agents and exogenous electrical stimulation, may provide a more receptive environment through which behavioral therapies may be imparted. This chapter reviews some of the recent results from animal models of injury and recovery that depict the complex time course of plasticity following cortical injury and implications for neurorehabilitation.