For half a century regions have been presented as engines and cradles of innovation. This chapter reviews the prolific development of academic concepts and logics and policy rationales dealing with this phenomenon. The review is based on a relational perspective, focusing on the role of vehicular ideas and unique regional development trajectories in nurturing (the image of) innovative regions. The core ideas are ‘new industrial spaces’, ‘territorial innovation models’ and ‘smart specialization’. This brings home two key contrasting points. On the one hand, regions are not only engines of innovation, but certain regions, notably those of an ‘outlier’ type, are the cradle of the very mechanisms of place-based innovation that shape such engines. On the other hand, too much emphasis on regions as innovation engines may result in a double trap, namely an economic ‘trap of endogeneity’ and a political ‘territorial trap’. Overcoming these traps still poses a major challenge.