ABSTRACT The literature on regional innovation systems has considerably enhanced our understanding of the critical role played by geographical proximity and local institutional conditions for the production of new knowledge and its economic exploitation. In most cases, however, both theoretical and empirical work has focused on regional innovation systems situated within a national context. Little research has been done so far on cross‐border regional innovation systems. The aim of this paper is to explore conceptually whether the theoretical approach of regional innovation systems can be applied to cross‐border settings. It investigates some critical conditions for the emergence of transfrontier innovation systems and concludes that cross‐border areas differ enormously regarding their capacity to develop an integrated innovation space.