Large river ecosystems worldwide are under increasing pressures from environmentally degrading processes related to population increase, land use changes, climate change and the release of chemical substances into the environment. The large spatial scale and a lack of empirical and theoretical understanding of the systems complicate environmental assessment in these systems. Recently, the Northern River Basins Study (NRBS) undertook a multi-disciplinary approach to assess environmental and socio-economic impacts of development in three large river basins in northern Canada; the Peace, the Athabasca and the Slave River. This paper provides the background and context for the NRBS and describes the rationale used in developing an assessment framework for the Study. An independent science advisory committee comprised of scientific experts from academia, First Nation and government oversaw quality assurance in terms of science planning, implementation and reporting. All technical studies were subject to both internal and external peer review prior to approval by a multi-stakeholder Study Board. The NRBS produced over 150 technical and 12 synthesis reports that detailed these findings and provided scientific recommendations. The Study Board used this information to prepare a final report and recommendations. The NRBS provides a clear example of a participatory, stakeholder approach that was successfully implemented in the design and management of an integrated watershed environmental assessment program.