This Policy Brief analyses the potential role of universities in the development and implementation of RIS3. Universities are often crucial institutions in regional innovation systems, especially in those with an absence of a dynamic, research led private sector, and there is rich history of academic and policy analysis in this area. However, with the new Smart Specialisation agenda, universities have a potentially pivotal role to play in its delivery. Yet there are a number of challenges and obstacles which must be considered, in addition to the numerous opportunities. This Policy Brief makes concrete suggestions on how universities can be integrated into RIS3 to deliver their desired economic and social outcomes.