Increased international attention to water resource management has resulted in the creation of new institutional arrangements and funding mechanisms as well as international initiatives designed to strengthen river basin institutions. The Global Environment Facility's (GEF) International Waters Program is at the heart of such novel collaborative regional approaches to the management of transboundary water resources. This paper assesses GEF-led efforts in the Danube River Basin, GEF's most mature and ambitious projects to date. It finds that GEF has been quite successful in building scientific knowledge and strengthening regional governance bodies. However, challenges of coordinating across expanding participants and demonstrating clear ecological improvements remain. GEF-led collaborative activities in the Danube River Basin reveal three critical lessons that can inform future river basin institution building and decision making, including the importance of appropriately creating and disseminating scientific data pertaining to the river system, the need for regional governance bodies for integrated river basin management, and the necessity to address coordination issues throughout project planning and implementation.