The concept of smart specialization has rapidly acquired a central position in European policy and academic circles. It raises interesting challenges for the regional studies agenda. First, smart specialization is about not only policy formulation, implementation and evaluation but also pooling scattered resources, competencies and powers to serve both shared and individual ambitions. Thus, policy formulation and implementation need to be seen in a new light. Second, when smart specialization is seen as one of the platforms for aligning several actors to boost regional economic development, the need to understand agency in its multiplicity emerges as central. This paper argues that to achieve truly transformative smart specialization strategies, there is a need to investigate in more depth the multi-actor strategy processes and new forms of leadership, as well as to invest time and money in advancing related capabilities across European regions.