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A systematic review of academic research and empirical studies on regional innovation systems reveals that the application and elaboration of this concept is fuzzy. The diversity of interpretation of the regional innovation system concept and its implementation as policy tool for economic development is neither clear nor readily operational, and their relationship with space is still matter of debate. The article intends to develop a reflection on the contributions and limits of this concept. The critique bears on the analytical framework and the institutional aspects of regional innovation, and the technological and industrial dynamics which allow to better understand the functioning of the innovation system.