While regional innovation systems are, to some extent, an artefact of regional administration and mimesis, there are also clear proximity and agglomeration dynamics. A third type of dynamic at play derives from uptake of knowledge production, regional role of universities etc. The advent of strategic science, with its double emphasis on relevance (including local relevance) and global competition, creates pressures on universities which want to play a regional role as well. The University of Twente, in The Netherlands, is an example. Its evolution shows that the regional function leans heavily on institutional differentiations like outreach units, while strategic science is taken up in new outward looking, problem-solving centres, not necessarily directed towards the region. The immediate moral is that universities can play a role in managing the tension between local (regional) and global, but the tensions will return internally. The general moral is that the changes in knowledge production (whether labeled as strategic science or Mode 2 or whatever) have to be taken into account in regional innovation systems. This might also help to avoid a short-sighted focus on wealth creation.