Wastewater systems are of crucial importance to the promotion of sustainable development. Through an integrated planning approach, the costs can be minimized and the resulting benefits maximized. A planning approach at regional level exploits the economies of scale, while achieving a better environmental performance. In this paper we set out a decision support approach for the planning of regional wastewater systems. Optimization models are used, aimed at finding optimal configurations for the location, type and size of the system's infrastructure: sewers, pump stations, and wastewater treatment plants. Solutions are evaluated in terms of the cost of installing, operating and maintaining the infrastructure, and the water quality in the river that receives the treated wastewater. The river water quality varies in accordance with the effluent discharges, and is assessed using environmental parameters. The models are solved with a simulated annealing algorithm complemented by a local improvement procedure. Its application is illustrated through a case study in the Una river basin region, in Brazil.