This report investigates the issues and challenges associated with identifying, calculating, and mapping indicators of the relative vulnerability of water quality and aquatic ecosystems, across the United States, to the potential adverse impacts of external forces such as long-term climate and land-use change. We do not attempt a direct evaluation of the potential impacts of these global changes on ecosystems and watersheds. Rather, we begin with the assumption that a systematic evaluation of the impacts of existing stressors will be a key input to any comprehensive global change vulnerability assessment, as the impacts of global change will be expressed via often complex interaction with such stressors: through their potential to reduce overall resilience, or increase overall sensitivity, to global change. This is a well established assumption, but to date there has been relatively little exploration of the practical challenges associated with comprehensively assessing how the resilience of ecosystems and human systems in the face of global change may vary as a function of existing stresses and maladaptations. The work described in this report is a preliminary attempt to begin such an exploration.