The concept of innovation systems has been a guiding paradigm of innovation research and strongly influenced research and innovation policy since the early 1990s. In spite of this success, criticisms have been raised in recent years about whether it is still a suitable framework for addressing the innovation-related challenges of the future. In the present paper we claim that systemic explanations of innovation success have still a very important role to play. In order to address the rising criticism, however, we have to reconsider the conceptual core of the family of innovation systems (IS) approaches and sketch out a path for renewal. The paper retraces the conceptual roots of IS approaches, assesses their uptake in different policy circles around the world, discusses the conceptual core and explanatory ambition, and finally formulates a future-oriented research agenda for a more integrative innovation systems framework.