Addressing the intertwined challenges of biodiversity loss and climate change requires rapid, intentional societal shifts. UNESCO Biosphere Reserves (BRs), established as interdisciplinary learning hubs for sustainable development, offer significant potential to bridge global commitments and local action. However, their effectiveness is hampered by structural, institutional, and perceptional/ideational challenges. This review identifies and categorizes these challenges, highlighting issues such as socioeconomic inequalities, governance constraints, and narrative complexities. Our analysis of 42 recent studies reveals that while BRs could serve as ‘living labs’ for transformative change, their impact is limited by these challenges. There are numerous indications that the development of BRs is at a critical juncture. If the identified challenges are not addressed, there is a risk that the role of BRs will be marginalized in the future, rather than evolving into key arenas that contribute to the transformative change we urgently need.