Beside the dominance of Belgrade in regional development of Serbia and marginal role of medium sized cities, macroregional centers were for a long time important carriers of economic development and a driving force of the overall prosperity. The objective of this work is to indicate the role of macroregional centers in the regional development of Serbia through their analysis and comparison of the results with the average values on the state level. Their existence represents a precondition for decentralization of Serbia. .