Multiple, interacting threats in a watershed creates challenges for natural resource management. Most watersheds experience multiple threats. Depending on the location, types, and intensity of interacting threats throughout the watershed, stream alterations are expected to vary along the network and through time, resulting in different biotic and ecosystem effects. Here, we depict only a few threats, alterations, and effects, with the overarching impact of climate change. There is limited understanding of the cumulative effects to ecosystem condition in the presence of multiple, interacting threats. It is critical to consider the spatial and temporal consequences of multiple threats and stressors throughout watersheds to advance improve management of multi-threat watersheds. DOI: https://doi.org/10.1525/elementa.256.f4