Integrated Water Resources Management (IWRM) is evolving as a contemporary means to address complex and critical issues associated with making the most effective and efficient use of water resources. Water resource challenges in the Zambezi River Basin include both quality and quantity issues including potential diversions from the basin to localities outside the basin and lack of an agreed upon institutional framework for the management of the Zambezi River system. In 1972, the United States and Canada signed the first Great Lakes Water Quality Agreement. This agreement committed the two countries who share the trans-boundary waters of the Great Lakes to restore and enhance water quality in the Great Lakes System. Amendments in 1987 resulted in establishing the goal to virtually eliminate persistent toxic substances into the Great Lakes resulting from human activities. In 2008, the Great Lakes Compact was approved by all of the eight Great Lakes States plus the Provinces of Ontario and Quebec. This compact was subsequently approved by the Congress of the United States and signed by President Bush on October 3, 2008. Both the Zambezi River Basin and the Great Lakes Basin offer valuable insights into the application of IWRM to critical water resource planning and management challenges in their respective geographical locations.