The Axios/Vardar River, an interboundary river located in the Balkan Peninsula, drains the region of southern Serbia, almost 80% of the Former Yugoslav Republic of Macedonia territory and some parts of northern Greece. This study is based upon long-term data (1979-2003) of nitrate, nitrite, ammonium, total phosphorous, BOD5. Cd, Cr, Zn, Pb and water discharge from 22 sampling stations along the Axios/Vardar River collected on a monthly basis. For determination of spatial and temporal trends, average values were determined for the periods 1979-83, 1984-88, 1990-95 and 1996-2003. Moreover, interviews with scientists from 10 institutions have been conducted in order to comprehend the situation that prevails in terms of water management. The quality of the river water is affected by heavy metal pollution from smelter and fertilizer plants in Veles, Ferro-alloys plant in Jegunovce, the disposal of their solid waste near the river bed and also by the untreated industrial wastewater discharge deriving from the industries located in the watershed. The agricultural runoff from cultivated areas of Tetovo, Veles and Koufalia is a significant source of nutrient pollution. The untreated domestic wastewaters discharged directly into Axios/Vardar River constitute point sources of pollution, as well as the illegal landfills contaminating the surface water and groundwater.