The statistics of cortico-cortical connectivity between the parietal and frontal lobes highlights the existence of different clusters of interconnected areas which shape the parieto-frontal system. The analysis of their functional properties allows the identification of few pillar domains spanning posterior parietal, anterior parietal, cingulate, frontal, prefrontal and orbitofrontal cortex. The inter-domains connectivity reveals different potential information processing streams, related to reaching, grasping, oculomotor intention and selective visual attention, action recognition, danger avoidance, selection of behavioral goals and strategies, as well as decision-making processes dependent on the predicted economic value of actions. These information processing lines are formed by long oligosynaptic pathways consisting of small myelinated axons carrying signals at low speed and with weak synaptic efficacy. Thus, information transfer between parietal and frontal areas seems to require significant spatial and temporal summation at post-synaptic level. These cortico-cortical connections are believed to be essential for motor learning. At the same time, the parieto-frontal system is characterized by a multiplicity of cortico-descending pathways, each transferring information at higher speed and with stronger synaptic efficacy than cortico-cortical ones. This rich outflow system, together with the different consequences of frontal and parietal lesions on cognitive-motor behavior, suggest that there probably exist in the cerebral cortex multiple local command sources and that the transition from planning to action does not always require the recruitment of primary motor cortex as a final cortical node for motor commands, but might be based on a direct access the peripheral motor apparatus, depending on task contingencies and affordances.