Motor system impairments are common after stroke and are a major contributor to disability after stroke. Most patients show improvement in the weeks-months following a stroke. Understanding the neurobiological underpinnings of these behavioral gains may be useful for refining treatments that aim to improve outcome and reduce disability. A number of brain mapping studies have examined how stroke affects motor system function. Numerous changes have been identified in this setting and are reviewed herein, including reduced laterality, widespread changes across a distributed sensorimotor network, and a change in the site and size of key activation foci. Some of these changes have been found to correlate with features of injury, behavior, or treatment-induced behavioral gains. A current challenge is to extend these findings to improve clinical decision making.