This review intends to begin to build a bridge between our understanding of the effect of motor rehabilitation and brain plasticity on recovery after hemiparetic stroke. It discusses the impact of intensive post-stroke motor rehabilitation on motor recovery. This is followed by an overview of our current understanding, based on human brain mapping technologies, of brain plasticity underlying spontaneous recovery after hemiparetic stroke. These discussions lead to a descriptive review of human brain mapping studies that have begun to provide an understanding of the neural basis of rehabilitation-induced gains in motor function after stroke. Finally, it speculates on how a solid understanding of the neural underpinnings of spontaneous and rehabilitation-induced motor recovery will permit brain mapping technologies to be applied toward optimizing post-stroke motor rehabilitation.