The purpose of this paper is, first, to highlight the role of the relationships between universities, institutions and firms in different regional development processes working towards a knowledge economy, and, second, to draw some implications for local policy makers. Adopting the regional innovation system (RIS) approach, the authors analyse selected regions -Cambridge (UK), Baden-Wurttemberg (Germany), Goteborg, (Sweden), Singapore, Milwaukee (USA) and Pittsburgh (USA) -which in the last two decades have undergone a process of economic and industrial renewal. From their analysis of the regional transformation process, they classify three different regional development paths defined respectively as 'RIS-into', 'RIS-from' and ` RIS-through' processes. Some common features emerge. In the process of regional development cooperation among universities, institutions and firms is essential. In particular, local universities play a crucial role in providing highly-educated people, research and spin-off activities. Thus universities are able to foster knowledge spillovers and interact constructively with firms. These interactions are nurtured and promoted by local policy makers.