Higher education institutions are undergoing a change in terms of conceptual and organizational models. Entrepreneurship and innovation in higher education are no longer only associated with start-ups and technology transfer, but are increasingly understood as core elements of a procedural framework for how organizations and individuals behave. This chapter presents HEInnovate, a joint initiative by the European Commission and the Organisation for Economic Co-operation and Development, which provides a guiding framework for higher education institutions and their partners in national and sub-national policy making entities to support innovation and entrepreneurship. The chapter argues that the benefit of a common guiding framework is in overcoming the common tendency of responding through silo structures confined to faculties and departments or specialized professional services (such as technology transfer centres), instead of a wider strategic response undertaken by the higher education institution as a whole. The chapter introduces the reader to the free online self-assessment tool that facilitates the implementation of institution-wide strategic responses. It also presents emerging findings from country reviews of Ireland, the Netherlands, Hungary and Bulgaria, undertaken as part of HEInnovate, and argues that there are cross-country commonalities in how higher education institutions define and implement their entrepreneurial agenda.