Climate change is poised to challenge the future persistence of aquatic organisms across the globe, and many uncertainties remain to whether, and if so how, species will cope. Here, we will explore how freshwater fishes may “persist in place” allowing them to survive in situ despite changing climates, or may “shift in space” by tracking of suitable bioclimatic conditions available in the future. This is accomplished by examining the mechanisms underlying large-scale variation in thermal tolerances (species’ sensitivity), investigating dispersal syndromes of freshwater fishes (species’ adaptive capacity), and integrating physiological estimates of thermal sensitivity with future climatic exposure to quantify global patterns of species’ vulnerability. These results highlight the urgency of global conservation actions and policy initiatives if harmful climate effects on the world’s freshwater fishes are to be mitigated in the future.