The aim of this study was to compile a new strategic framework to guide the funding and management of research in water-related human health in South Africa. This framework had to identify the research areas of highest need in the country and provide an effective, yet simple, tool for the management of research projects. A review of current water-related human health research was first undertaken. Using this review as background document, input was solicited from key people in Government, water boards, metro councils, science councils and universities. As part of the study, the country's research support infrastructure for water-related health research was investigated. The framework was finalised at a stakeholder workshop. A structure of Thrust Areas, with Programmes under each Thrust Area, was suggested for research management and funding. A matrix system of research thrusts versus impacts / risks, interventions and governance was further constructed to assist in the identification of research gaps, rendering the framework a very useful tool in the funding and management of water-related human health research.