The Serbian National Waste Management Strategy for the Period 2010-2019, harmonized with the European Union Directives, mandates new and very strict requirements for landfill sites. To enable analysis of a number of required qualitative and quantitative factors for landfill site selection, the traditional method of site selection must be replaced with a new approach. The combination of GIS and the Analytic Hierarchy Process (AHP) was selected to solve this complex problem. The Srem region in northern Serbia, being one of the most environmentally sensitive areas, was chosen as a case study. Seventeen factors selected as criteria/sub-criteria were recognized as most important, divided into geo-natural, environmental, social and techno-economic factors, and were evaluated by experts from different fields using an AHP extension in Arc GIS. Weighted spatial layers were combined into a landfill suitability map which was then overlapped with four restriction maps, resulting in a final suitability map. According to the results, 82.65% of the territory of Srem is unsuitable for regional landfill siting. The most suitable areas cover 9.14%, suitable areas 5.24%, while areas with low and very low suitability cover 2.21 and 0.76% of the territory, respectively. Based on these findings, five sites close to two large urban agglomerations were suggested as possible locations for a regional landfill site in Srem. However, the final decision will require further field investigation, a public acceptance survey, and consideration of ownership status and price of the land.