Innovation districts are being implemented as urban regeneration strategies in cities as diverse as Barcelona (Spain), Boston (Massachusetts), Chattanooga (Tennessee), Detroit (Michigan), Medellín (Colombia), and Montréal (Canada). Little, however, is known about the concept. This paper aims to provide a framework to define innovation districts. The research methodology is based on a qualitative approach using 22@ Barcelona as single case study. 22@ Barcelona was the first planned innovation district and has been a model for the innovation districts of Medellín (Colombia) and Boston (Massachusetts) among others. The paper finds that innovation districts based on the 22@ Barcelona’s model are designed around four strategic dimensions, namely urban planning, productive, collaborative, and creative, all coordinated under a strong leadership. An innovation district is a place-based urban development strategy that aims to regenerate an under-performing downtown neighborhood into a desirable location for innovative and creative companies and workers.