The purpose of this study was to examine the time course of changes in cerebral activity and functional connectivity during long-term adaptation to a visuomotor transformation. Positron emission tomography was used to measure changes in brain activity as subjects tracked a target under the influence of a rotational transformation that distorted visual feedback. The experiment was one-week long and consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining early and late stages of learning. On average, visuomotor adaptation was achieved within three days. During early stages of adaptation, better performance was associated with greater activity in brain areas associated with attention including bilateral dorsolateral and ventrolateral prefrontal cortices, frontal eye fields, and the human homologue of area MT. However, as adaptation proceeded, improvements in performance were associated with greater activity in motor regions such as the left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left cingulate motor area, right putamen and a non-motor region within the middle temporal gyrus. This learning-specific shift in brain activity was associated with a progressive change in the functional connectivity of these regions towards the end of the first session. Interestingly, only the functional connections between the anterior cerebellum, left middle temporal gyrus and left sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our findings suggest that visuomotor adaptation is not only reflected in persistent changes in activity in motor-related regions but also in the strengthening and maintenance of specific functional connections.