Description The Smart Specialization Strategy (S3) is a central pillar of the Europe 2020 Strategy. The implementation of S3 requires EU regions to identify technological domains in which they are more likely to reach or maintain a competitive advantage, and then focus their investment and innovation policy in those domains. The concept of S3 is based on two fundamental ideas: a) that a region should avoid spreading investments across many different fields, but concentrate them in a few sectors or technological domains in which they can have a significant impact (specialisation); b) that those domains are not to be chosen because of their technological or market appeal but because they enhance or complement the research and productive assets already present in the region (smart). S3 represents a relevant novelty for regional innovation policy. However, it also poses several challenges for its effective implementation.