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This review describes our current understanding of the changes in brain function and structure that occur in response to an intensive form of motor rehabilitation, constraint-induced movement therapy (CIMT), that has been shown to be efficacious in promoting motor function of the paretic upper limb of stroke patients.Studies using transcranial magnetic stimulation have demonstrated consistently an increase in the size of the representation of paretic hand muscles in the ipsilesional motor cortex after CIMT. This motor map expansion occurs in response to CIMT delivered at all time periods after stroke, from within days to after several years. Functional neuroimaging studies have shown varying patterns of change in activation within the sensorimotor network after CIMT. This variability may depend on the extent of stroke-induced damage to the corticospinal tract, the major descending motor pathway in the brain. This variability may also stem from interacting plastic changes in brain structure occurring in response to CIMT.CIMT is the first well defined poststroke motor rehabilitation to have identified changes in brain function and structure that accompany gains in motor function of the paretic upper limb. However, a causal link between observed changes in brain function/structure and motor gains due to CIMT has not yet been established. There is still much work to be done to understand the relationship between changes in brain function/structure and gains in motor function. Such studies should employ rigorous experimental controls to enable strong conclusions to be drawn regarding the neural effects of CIMT and how those effects confer behavioral efficacy of the therapy.