Southern Africa is characterized by a large number of international river basins, inherent climatic variability, and a natural maldistribution of perennial rivers. The region also has a history of political instability, driven by liberation struggles against the former colonial powers and the Cold War. Southern Africa’s transboundary rivers and their associated ecosystems could become either drivers of peace and economic integration or sources of endemic conflict. Water scarcity has also placed limits on the future economic growth potential of the region’s four most economically developed countries. This situation, combined with the regional development of international and increasingly complex interbasin water transfers, highlights the need to develop appropriate scientific methodologies that can explain and predict future patterns of conflict and cooperation.