Fifteen major Balkan rivers with over 80% of the inflows in Eastern Mediterranean were examined for their environmental state within the DPSIR framework. Physicogeographic and hydrochemical conditions differ substantially among river basins, which may be roughly classified into three main zones. Despite strong fragmentation, most of the rivers are liable to flash floods and have low summer flow. Decreasing precipitation and (mis)management caused a dramatic discharge reduction over the last decades. Wars, political instability, economical crises over the past decades, combined with administrative and structural constraints, poor environmental planning and inspection and, frequently, a lack of environmental awareness imposed significant pressures on rivers. Large wetland areas were drained in favour of widespread intensive agriculture. The treatment of municipal wastewaters is barely adequate in Greece and insufficient elsewhere, while management and treatment of mining and industrial wastewaters is overall poor. In general, lowland river sections are hydro-morphologically modified and are at the greatest pollution risk, while upstream areas mostly retain their natural conditions. Nutrient concentrations in a number of central and eastern Balkan rivers often exceed quality standards, whereas pesticides and heavy metals, partly of geochemical origin, occasionally exceed quality standards. Reservoirs retain vast masses of sediments, thus adversely affecting delta evolution, while dam operation disturbs the seasonal hydrological and hydrochemical regimes. Almost all Balkan countries face daunting water resource challenges because of urgently needed investments in water supply, sanitation, irrigation, and hydroelectricity. International treaties and designations and European Union Directives have mobilized pollution mitigation and conservation efforts. However, the application of environmental legislation has proved in a number of cases inadequate. Constraints arise from long-standing top-down planning traditions, inadequate planning of national environmental policies, poor administrative capacities, and heavy investment requirements, often combined with a lack of environmental awareness.