It is argued in the paper that Regional science needs to rethink its theoretical frameworks and research agendas. Globalization and impending recession show starkly how too little attention has been paid to issues of finance and the supply of funds within economies. Too frequently business relationships have been seen as embedded in benign networks, neglecting issues of power, control and exclusion, the role of contracts and their enforcement, and the pursuit of inimitability to maximise rents. Rethinking these issues involves new perspectives to be developed on policy development, including the neglected significance of ‘bureaucratic politics’, and how policy interacts with communities to create outcomes on the ground. The paper seeks to stimulate a debate that is needed to keep Regional Science relevant.