Global climate change affects stream and river ecosystems in various ways, including hydrologic regime, temperature regime, sediment and nutrient runoff, and others with as yet difficult to predict regional variations.  This will have consequences to state and tribal environmental resource managers who rely on assessment using biological indicators to determine impairment and establish probable causes.  The ability to discern impairment using biological indicators is largely reliant on a comparison to reference conditions.  As climate change progressively affects aquatic ecosystems, the continued ability to accurately detect impairment due to other stressors will be impacted by climate-mediated changes in reference and impaired conditions, and by potential interactions between direct climate effects and other stressors.  Potential biological responses, including loss of sensitive taxa, increases in abundance of tolerant taxa, and others, may decrease signal-to-noise ratios, with a corresponding decrease in the ability to detect impairment from non-climate (e.g., regulated) stressors when it really exists.  We explored the ability of existing analytical approaches to identify stressors under different scenarios of climate change, to help control for climate change effects.  The approaches explored gave varied results, depending on the response scenario selected.  These highlight the need for careful consideration of assessment program designs.