Background—The precise mechanisms of and biological basis for motor recovery after stroke in adults are still largely unknown. Reorganization of the motor system after stroke as assessed by functional neuroimaging is an intriguing but challenging new field of research. Provocative but equivocal findings have been reported to date.Summary of Review—We present an overview of functional neuroimaging studies (positron emission tomography or functional MRI) of motor tasks in patients recovered or still recovering from motor deficit after stroke. After a brief account of the connectivity of motor systems and the imaging findings in normal subjects, the literature concerning stroke patients is reviewed and discussed, and a general model is proposed.Conclusions—Both cross-sectional and longitudinal studies have demonstrated that the damaged adult brain is able to reorganize to compensate for motor deficits. Rather than a complete substitution of function, the main mechanism underlying recovery of motor abilities involves enhanced activity in preexisting networks, including the disconnected motor cortex in subcortical stroke and the infarct rim after cortical stroke. Involvement of nonmotor and contralesional motor areas has been consistently reported, with the emerging notion that the greater the involvement of the ipsilesional motor network, the better is the recovery. This hypothesis is supported by the enhanced activity of the ipsilesional primary motor cortex induced by motor training and acute pharmacological interventions, in parallel with improved motor function. Further longitudinal studies assessing the relationships between such changes and actual recovery, as well as manipulating such changes by rehabilitation or pharmacological maneuvers, should provide further information on these fundamental questions. This review closes with some perspectives for future research.