Regional innovation agencies are established across the OECD to deliver innovation policies at sub-national level. Various agency models are possible. This chapter illustrates the diversity of models in practice, highlights success conditions to achieve a new paradigm for innovation and regions, and discusses the key strategic challenges agencies face. Their primary challenge is to serve as change agents for the regional innovation system. They need to focus on absorptive capacities and learning processes, both for their policy targets and management of the agency itself.