The extensive application of fMRI to the assessment of the human sensorimotor system has disclosed a complexity that is largely beyond our original understanding. From the available data, it is accepted that this system consists of a large, and somewhat yet unknown, number of cortical and subcortical areas, with a precise location and a specialized function. In particular, a large number of regions in the frontal and parietal lobes contribute to different aspects of motor act performance. It is also evident that the properties and potentialities of this network still need to be fully elucidated by further research. Defining how the human sensorimotor system works is of outmost importance for understanding its dysfunction in case of diseases and also to develop potential therapeutic strategies capable to enhance its functional plasticity and reserve.