We investigated neural effects of visuo-motor discordances during visually-guided finger movements. An fMRI-compatible data glove was used to actuate (in real-time) virtual hand models shown on a display in 1^st person perspective. In experiment 1, we manipulated virtual hand motion to simulate either hypometric or unintentional (actuation of a mismatched finger) feedback of sequential finger flexion in healthy subjects. Analysis of finger motion revealed no significant differences in movement behavior across conditions, suggesting that between-condition differences in brain activity could only be attributed to varying modes of visual feedback rather than motor output. Activation in the veridical relative to either altered feedback conditions was localized to the ipsilateral motor cortex. Hypometric feedback and mismatched finger feedback (relative to veridical) were associated with distinct activation. Hypometric feedback was associated with activation in the contralateral motor cortex. Mismatched feedback was associated with activation in bilateral ventral premotor, left dorsal premotor and left occipitotemporal cortex. The time it took the subject to evaluate visuomotor discordance was positively correlated with activation in bilateral supplementary motor area, bilateral insula, right postcentral gyrus, bilateral dorsal premotor areas and bilateral posterior parietal lobe. In Experiment 2, we investigated the effects of hypo- and hypermetric visual feedback in three stroke subjects. We observed increased activation of ipsilesional motor cortex in both hypometric and hypermetric feedback conditions. Our data suggest that manipulation of visual feedback of one’s own hand movement may be used to facilitate activity in select brain networks. We suggest that these effects can be exploited in neurorehabilition to enhance the processes of brain reorganization after injury and, specifically, might be useful in aiding recovery of hand function in patients during virtual reality-based training.