A significant challenge of our time is conserving biological diversity while maintaining economic development and cultural values. The United Nations Educational, Scientific and Cultural Organization has established biosphere reserves within its Man and the Biosphere program as a model means for accomplishing this very challenge. The East Carpathians Biosphere Reserve (ECBR), spreading across Poland, Slovakia, and Ukraine, represents a large social-ecological system (SES) that has been protected under the biosphere reserve designation since 1998. We have explored its successes and failures in improving human livelihoods while safeguarding its ecosystems. The SES framework, which includes governance system, actors, resources, and external influences, was used as a frame of analysis. The outcomes of this protected area have been mixed; its creation led to national and international collaboration, yet some actor groups remain excluded. Implementation of protocols arising from the Carpathian Convention has been slow, while deforestation, hunting, erosion, temperature extremes, and changes in species behavior remain significant threats but have also been factors in ecological adaptation. The loss of cultural links and traditional knowledge has also been significant. Nevertheless, this remains a highly biodiverse area. Political barriers and institutional blockages will have to be removed to ensure this reserve fulfills its role as a model region for international collaboration and capacity building. These insights drawn from the ECBR demonstrate that biosphere reserves are indeed learning sites for sustainable development and that this case is exemplary in illustrating the challenges, but more importantly, the opportunities that arise when ensuring parallel care and respect for people and ecosystems through the model of transboundary protected areas around the world.