Evidence exists that the observation of actions activates the same cortical motor areas that are involved in the performance of the observed actions. The neural substrate for this is the mirror neuron system. We harness this neuronal system and its ability to re-enact stored motor representations as a means for rehabilitating motor control. We combined observation of daily actions with concomitant physical training of the observed actions in a new neurorehabilitative program (action observation therapy). Eight stroke patients with moderate, chronic motor deficit of the upper limb as a consequence of medial artery infarction participated. A significant improvement of motor functions in the course of a 4-week treatment, as compared to the stable pre-treatment baseline, and compared with a control group have been found. The improvement lasted for at least 8 weeks after the end of the intervention. Additionally, the effects of action observation therapy on the reorganization of the motor system were investigated by functional magnetic resonance imaging (fMRI), using an independent sensorimotor task consisting of object manipulation. The direct comparison of neural activations between experimental and control groups after training with those elicited by the same task before training yielded a significant rise in activity in the bilateral ventral premotor cortex, bilateral superior temporal gyrus, the supplementary motor area (SMA) and the contralateral supramarginal gyrus. Our results provide pieces of evidence that action observation has a positive additional impact on recovery of motor functions after stroke by reactivation of motor areas, which contain the action observation/action execution matching system.