In the present paper, the possibility of the treated municipal wastewater (TMWW) reuse in agriculture, produced by the Wastewater Treatment Plants of Aitoloakarnania prefecture, one of the greatest agricultural regions of Greece, has been investigated. The boundaries of agricultural soils and the irrigated crops were defined, and the water requirements of crops were calculated. Also the chemical characteristics of the TMWW were determined for the safe reuse in crop production, and for the protection of soils from potential pollution. The research conducted in this area is expected to constitute the basis for an integrated TMWW reuse planning in soils and crops, in the context of sustainable agriculture, and environmental protection. It must be mentioned that the Messolongion-Aitolikon lagoon is in the area under investigation, one of the largest wetland ecosystem of Mediterranean region, which makes the area ecologically sensitive. The ultimate scope of this study is to describe the planning of the TMWW reuse on the basis of soil characteristics, climatic factors, and irrigation water requirements of the crops, grown in this ecologically sensitive area. The volume of the effluents produced by the wastewater treatment plants of Messolonghion, Agrinion, Nafpaktos, Aitoliko and Thermo could cover 19.3%, 25.14%, >100%, 17.18 and 87.84% of the irrigation water requirements, respectively.