Central Asia contains one of the largest internal drainage basins in the world, and its continental location results in limited availability of both surface and groundwater. Since the twentieth century, water resources of the region have been exploited beyond sustainable levels. From small Mongolian headwater streams to the mighty Aral Sea, surface waters have been partially desiccated. Demands from the agricultural, energy and raw material sectors as well as population growth have not only increased water abstractions, but also left a diverse and strong pollution footprint on rivers, lakes and groundwater bodies. Such changes in water quantity and quality have not only led to a degradation of aquatic and riparian ecosystems, but also they have placed the region’s socioeconomic development at risk. Because of the complexity of Central Asia’s water problems, integrated assessment and management approaches are required. Despite some shortcomings in practical implementation, the widespread adoption of the Integrated Water Resources Management and water–food–energy nexus approaches may be keys to a more sustainable future. This thematic issue aims to provide documentation of the current state of scientific knowledge, ranging from hydrological research to water quality investigations, and offers an assessment of ecosystems and the services provided by them. Reviews and case studies on different management options conclude the thematic issue by providing insights into field-tested solutions for the region’s water challenges.