The Istanbul Metropolitan Area is located in a very critical area between the Marmara Sea, the Bosphorus and the Black Sea. Recent investigations clearly indicate that the Marmara Sea now possesses all the striking properties of a sensitive zone. Therefore the nature and the magnitude of wastewater treatment and disposal is a major factor to be considered for the protection of the Marmara Sea. Conversely, wastewater management in Istanbul should be carefully defined and optimized on the basis of the delicate hydrodynamic and ecological balance between the adjacent seas. The paper critically reviews all related findings to provide a scientific basis for major factors requiring specific emphasis in a wastewater management program for Istanbul. In this framework, highly controversial issues, such as need for nutrient removal for discharges to the Marmara Sea, degree of treatment required around Bosphorus and the junction zone, and the location of Kadiköy and Riva discharges are critically evaluated in the light of the existing scientific evidence.