The Basque Country region in Spain is world renowned for a successful industrial transformation, the urban regeneration of Bilbao, cultural distinctiveness, unique governance arrangements and high wealth levels. Over the last 30 years, the region has implemented its science, technology and innovation (STI) policy driven by a need to boost industrial competitiveness. The role of total factor productivity and innovation in driving growth was significant in the 1990s and declined in the early part of this decade, but appears to be on the rise again thanks in part to significant increases in public and private investment in innovation. The Basque Country has begun a transition from a model of incremental innovation in manufacturing to a model increasingly based on science and other forms of knowledge. Through a diagnostic of the innovation system and the policy mix, the review offers some policy and governance recommendations to achieve the region’s desired transition in light of global trends in the innovation process and innovation policy.