Urban streams commonly express degraded physical, chemical, and biological conditions that have been collectively termed the “urban stream syndrome”. The description of the syndrome highlights the broad similarities among these streams relative to their less-impaired counterparts. Awareness of these commonalities has fostered rapid improvements in the management of urban stormwater for the protection of downstream watercourses, but the focus on the similarities among urban streams has obscured meaningful differences among them. Key drivers of stream responses to urbanization can vary greatly among climatological and physiographic regions of the globe, and the differences can be manifested in individual stream channels even through the homogenizing veneer of urban development. We provide examples of differences in natural hydrologic and geologic settings (within similar regions) that can result in different mechanisms of stream ecosystem response to urbanization and, as such, should lead to different management approaches. The idea that all urban streams can be cured using the same treatment is simplistic, but overemphasizing the tremendous differences among natural (or human-altered) systems also can paralyze management. Thoughtful integration of work that recognizes the commonalities of the urban stream syndrome across the globe has benefitted urban stream management. Now we call for a more nuanced understanding of the regional, subregional, and local attributes of any given urban stream and its watershed to advance the physical, chemical, and ecological recovery of these systems.