Mediterranean endemic freshwater fish are among the most threatened biota in the world. The Mediterranean basin has experienced substantial reductions in precipitation and water availability, which will worsen with climate change. Current water policy is directed to increase water-supply demands, especially for agriculture, and not to improve water-use efficiency and implement integrated and sustainable water management. Illegal extractions are common, exacerbating problems for important protected areas. Management is needed to mitigate the conflicts between environmental water and human demand, and ensure availability of water to maintain ecological processes and Mediterranean freshwater biodiversity. Water availability is not the only threat, although it is exacerbated by pollution and invasive species. The uneven spatial distribution of threats across the Mediterranean basin requires different strategies to conserve freshwater biodiversity. Implementation of multi-national laws (e.g. Water Framework Directive in the European Union) will help future management of freshwater ecosystems. Management actions must be planned at whole-catchment scales, with collaboration among different countries and water-management authorities. The current reserve area is small compared with other areas in the world and driven by terrestrial interests, and should be evaluated for its effectiveness to protect the Mediterranean freshwater biodiversity.