The authors provide a science-based assessment of current and future scenarios of water availability, the demands of key sectors, including agriculture and hydropower, and the environment under changing demographic, economic, social and climatic conditions. They also identify solutions and strategies that will allow available water resources to be sustainably used to improve agricultural productivity, food security and economic growth in the VRB. Overall, the work examines from a multidisciplinary and multi-stakeholder perspective the solutions and strategies to improve the use of water and other natural resources in the VRB to achieve enhanced food security, livelihoods and economic growth.