Most Great River ecosystems (GREs) are extensively modified and are not receiving adequate protection to prevent further habitat degradation and loss of biotic integrity. In the United States, ecological monitoring and assessment of GREs has lagged behind streams and estuaries, and the management of GREs is hampered by the lack of unbiased data at appropriate spatial scales. Properties of GREs that make them challenging to monitor and assess include difficult sample logistics and high habitat diversity. The U.S. Environmental Protection Agency's Environmental Monitoring and Assessment Program (EMAP) has developed a comprehensive, regional-scale, survey-based monitoring approach to assessment of streams and estuaries, but has not yet conducted research on applying these tools to GRE monitoring. In this paper we present an overview of an EMAP research project on the Upper Missouri River (UMR). We summarize the assessment objectives for the study, the design for selecting sample locations, the indicators measured at these sites and the tools used to analyze data. We present an example of the type of statements that can be made with EMAP monitoring data. With modification, the set of methodologies developed by EMAP may be well suited for assessment of GREs in general.