While innovation should be about socioeconomic transformation of society, concerns have been raised about its negative externalities including growing disparities within and between regions. Arguably, Responsible Research and Innovation (RRI) offers a potential solution to address these concerns. However, in theory, its conceptualization and operationalization remain ambiguous. Further, in practice, this makes its application to regional development difficult. Accordingly, this study first conducts a systematic literature review of conceptual papers on RRI. It identifies themes and categorizes them into four domains: drivers, tools, outcomes and barriers. Second, these domains are applied to regional innovation studies. The paper contributes to an increased understanding of RRI and its applications to sustainable regional development as well as how RRI and regional innovation studies can benefit from each other.