Abstract Transboundary waters are some of the most economically, important, highly stressed, and humanly populated areas on earth. For, over two decades, the Global Environment Facility (GEF), through its, International Waters (IW) Focal Area, has been providing incremental cost, finance to aid developing countries and countries in transition to jointly manage these freshwater basins and Large Marine Ecosystems (LMEs) sustainably. Critical to this aim is a strong basis in scientific knowledge, and ongoing research to inform the development and implementation of projects. This paper provides a brief introduction to GEF IW, the challenges being faced that relate to the science–policy interface, and the processes that have been employed by the GEF to cope with these challenges. Examples from the global portfolio of the GEF IW projects are highlighted to illustrate the use of sound and appropriate science, engagement of local science communities, and a necessary focus on social science issues to catalyze institutional development and on-the-ground action. The importance of the IW:Science project for the GEF is outlined, and the implication of this work for future programming of GEF transboundary water projects is discussed.