Freshwater environments and their fishes are particularly vulnerable to climate change because the persistence and quality of aquatic habitat depend heavily on climatic and hydrologic regimes. In Australia, projections indicate that the rate and magnitude of climate change will vary across the continent. We review the likely effects of these changes on Australian freshwater fishes across geographic regions encompassing a diversity of habitats and climatic variability. Commonalities in the predicted implications of climate change on fish included habitat loss and fragmentation, surpassing of physiological tolerances and spread of alien species. Existing anthropogenic stressors in more developed regions are likely to compound these impacts because of the already reduced resilience of fish assemblages. Many Australian freshwater fish species are adapted to variable or unpredictable flow conditions and, in some cases, this evolutionary history may confer resistance or resilience to the impacts of climate change. However, the rate and magnitude of projected change will outpace the adaptive capacities of many species. Climate change therefore seriously threatens the persistence of many of Australia’s freshwater fish species, especially of those with limited ranges or specific habitat requirements, or of those that are already occurring close to physiological tolerance limits. Human responses to climate change should be proactive and focus on maintaining population resilience through the protection of habitat, mitigation of current anthropogenic stressors, adequate planning and provisioning of environmental flows and the consideration of more interventionist options such as managed translocations.