Book excerpt: Over the past 25 years, the regional innovation system (RIS) approach has become a powerful framework for explaining the uneven geographical distribution of innovation in space as well as for developing policies geared towards boosting the innovation capability of regional economies. This Advanced Introduction provides a critical review and discussion of research on RIS to answer a set of core questions covering the origins of the concept and its theoretical underpinnings to the challenges for future scholarly work on RIS.