This chapter aims at investigating how local innovation systems may relate to other economic systems thanks to a set of channels which make regions proximate along several dimensions. In particular, we assess if, and how much, the creation of new ideas in a certain region is the result of internal efforts as much as knowledge flows coming from other regions which may be considered neighbours not only in the geographical space but also in the institutional, technological, social and organizational one. Our discussion is based on the results of spatial econometric analysis applied to the EU regional systems of innovation which offers some specific and some general readings. Results attest the importance of regions’ capability in exploiting relationships with close-by regions in the geographical space but also proximate regions in the technological space which may prove geographically very distant. This implies that, no matter whether the knowledge flow is due to collaborations, imitation or workers mobility, there is a global perspective which goes beyond the regional and the national systems of innovation. Global networks which connect regions which share the same specialization and therefore the same cognitive and technological base may be as crucial as local cluster of regions in enhancing technological advance. On the whole, regional system of innovations have to be effective not only in exploiting their internal production of ideas based on R&D investments and human capital but also in creating synergies with other regions to absorb part of their knowledge and expertise.