Functional recovery after brain damage or disease is dependent on the neuroplastic capability of the cortex and the nonaffected brain. Following cortical injury in the motor and sensory regions, the adjacent spared neural tissues and related areas undergo modifications that are required in order to drive more normal motor control. Current rehabilitation models seek to stimulate functional recovery by capitalizing on the inherent potential of the brain for positive reorganization after neurological injury or disease. This article discusses how neuroimaging and electrophysiological data can inform clinical practice; representative data from the modalities of functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, electroencephalography, and positron emission tomography are cited. Data from a variety of central nervous system disease and damage models are presented to illustrate how rehabilitation practices are beginning to be shaped and informed by neuroimaging and electrophysiological data.