Territorial, economic and social cohesion in European Union (EU) regions are major challenges that regional policies are aimed at. These policies have a strong focus on innovation-driven models as key processes for reducing disparities and promoting regional development. Since the 1980s, innovation and technology policies have gained momentum and legitimacy to stimulate multiple development patterns and growth models, mainly from national economic dynamics to well performing regional systems. Theories of knowledge and learning have been developed in more successful places, producing concepts that seem unattainable for less successful ones. Given that less developed regions have been overlooked in innovation studies, this paper reviews the literature on territorial innovation models in Europe in order to understand theoretical and practical gaps for these regions and to identify trends that support the need to redirect conceptual, political and instrumental attention of territorial innovation systems. It debates the different forms of innovation in regions, the variety and role of actors, the quest for geographical and place-based resources, the determinants for innovation and the ‘how’ and ‘for what’ demands of regional development. The discussion anticipates critical questions that try to promote a ‘normative turn’ in innovation policy, propose research avenues and discuss policy implications.