While the evidence base on successful practices in knowledge exchange is rapidly growing, much less attention has been given in the academic literature to documenting and reflecting on failures in trying to exchange different types of evidence between academics, practice partners and policymakers. However, learning from failures is just as important, if not more crucial, than celebrating successes. Therefore, in this introduction to the special issue on learning from failures in knowledge exchange, we discuss crosscutting themes across the seven papers. We start by comparing and theorising different definitions of failures, and by exploring the relational barriers and structural stressors underlying these failures. We argue for the creation of a ‘failure culture’ in organisations, in which failures are no longer avoided but actively encouraged. To turn failures into successes, we identify a need for more sharing and publishing of failures, early engagement with stakeholders in the knowledge exchange process, and illustrate the importance of boundary spanners. We conclude with recommendations for future work, related to promising theoretical approaches, such as system thinking, the re-addressing of power imbalances through leadership, and highlight art-based approaches as a mechanism for rebalancing power.