Based on the empirical findings achieved through comparative research involving 40 innovation policy instruments from 11 European regions, this paper proposes a shift in rationale and in the broad orientations of innovation policy to focus on addressing SMEs in their regional context. The main role for innovation policy, which aims to increase the capacity of a region and the capabilities of its SMEs to innovate, is to foster interactive learning within the firms and within the region. This calls for an interactive mode of policy intervention. The paper deals also with the question of how to build a coherent portfolio of policy instruments, taking into account both regional situations and specific SMEs needs in terms of innovation. The key message is that there is no 'one-size-fits-all' policy portfolio. Regional differences in innovation capabilities call for a tailored mix of policy instruments. One salient element of the conclusion is the need for more 'policy intelligence' in this complex field.