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The paper deals with the control of a wastewater treatment plant designed for a 250,000 inhabitants city. In order to developed different control strategies a specific influent was defined. It is the influent from BSM1 calibrated according to the real data of the wastewaters collected from the wastewater treatment plant. Five control strategies were developed based on conventional controllers and compared to each other using the quality indicators specific to the wastewater treatment domain. Finally, an optimal setpoint-based control method has been developed which takes into consideration a criterion based on two very important factors in the case of a large-capacity wastewater treatment plant: the cost of the biological treatment and the effluent quality.