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Operating at the science, policy, practice interface (SPPI) is often contentious, as knowledge creators and end-users seldom engage, preferring to operate in their own worlds. The application of science to solve sustainability challenges has not received the desired attention, especially in developing countries. How to strengthen the credibility, relevance and legitimacy of research so as to enhance the chances of uptake in decision making? How to generate knowledge differently, so that it is more likely to bring about change and benefit society? The purpose of this research is to examine these questions in the context of three sustainability case studies that were able to transcend the knowledge action barrier. These case studies are from the global biodiversity hot spot of Eastern Himalaya, India, and cover the themes of sustainability of pastoral systems, promoting sustainable livelihoods for the poor and co-designing a Himalayan spring revival initiative. The findings are structured to highlight how the demand for science arose, findings of the research and how the knowledge generated was translated into action. The results show that firstly relevance of science increases manifold when aligned to prominent policy decisions and real-world problems. Secondly, trans-disciplinary studies that synthesize social, economic and ecological aspects have a greater chance of influencing policy makers. Thirdly, mediation by science stewards holds lot of promise in connecting the worlds of academicians and policy makers. The study provides practical guidance on bridging the SPPI and contributes to the growing body of the literature on sustainability science.