Chapter 2 introduces an evolutionary economic perspective to regional development in peripheral regions, focusing on lock-in, renewal, path-breaking, and path-switching. The chapter proposes the idea of regional innovation coalitions as bodies purposively influencing regional development trajectories, highlighting universities’ complex roles as knowledge developers and transmitters within those coalitions. The chapter also sets out the possible tensions facing regions such as knowledge mismatch and communications problems, to produce a threefold classification of potential contributions, as the basis for the empirical chapters’ conceptual basis. These three processes are (a) universities as institutional actors in the periphery, (b) universities as knowledge match makers and innovators, and (c) universities as creators of entrepreneurial support activities.