Universities play an important role in the knowledge based economy, and are key regional actors, providing knowledge, resources and human capital. Border regions are a specific type of peripheral region, often peripheral in terms of distance to the centre and national governments. But even in centrally located border regions developing integrated cross-border region is mostly often deemed less important than regional and national issues. Many most border regions may benefit from building-up cross-border connections and developing systemic interactions between actors over the border. Universities can play an important role in shaping regional innovation systems, and cross-border regions are interesting because of this inherent fragmentation. We explore universities’ role that universities can play in cross-border regions, in terms of developing linkages to other sectors (business, public sector) and linkages over the border. On this basis we develop a conceptual typology for university involvement in cross-border regions.