Smart specialisation is the most ambitious regional innovation programme ever to be launched in the European Union and it affords a unique opportunity to explore the interplay between institutions, innovation and development. The article argues that smart specialisation makes unprecedented demands on public sector bodies to nurture more collaborative forms of economic search and craft more inclusive forms of regional governance. To explore these issues with the granularity they deserve, the article offers detailed case studies of two regional innovation policy repertoires in Wales and the Basque Country, where it is argued that the ‘old industrial region’ moniker conceals as much as it reveals because, for all their apparent similarities, they have pursued very different repertoires. The article concludes on a more general note by suggesting how regional innovation studies could be enriched by engaging with theoretical perspectives from other fields.