In the last decade, many studies confirmed the benefits of mental practice with motor imagery. In this review we first aimed to compile data issued from fundamental and clinical investigations and to provide the key-components for the optimization of motor imagery strategy. We focused on transcranial magnetic stimulation studies, supported by brain imaging research, that sustain the current hypothesis of a functional link between cortical reorganization and behavioral improvement. As perspectives, we suggest a model of neural adaptation following mental practice, in which synapse conductivity and inhibitory mechanisms at the spinal level may also play an important role.