Climate change and a growing population around the Mediterranean Rim are increasing the need for water and, consequently, the pressure on resources in terms of both quantity and quality. High-quality water should be primarily reserved to drinking water while reclaimed water is an alternative for other usages. A review of situations in Tunisia, Jordan, France, and Italy involving the use of reclaimed water highlights the disparity in national regulations governing this alternative water resource and in its management. On the first hand, the use of recycled water for irrigation can have an adverse impact on public health and the environment, depending on treatment and irrigation practices. On the other hand, it may also represent a new source of water: wastewater should no longer be considered as waste but, rather, as a new resource to be handled in a circular economy-type loop. Current scientific knowledge in agronomic and environmental sciences, as well as in the economic and social sciences, can be integrated and used to lower the associated risk through the effective management of irrigation using recycled water and to address the following questions: (i) How can the time-varying nutrient needs of crops be managed to operate safe environmental reuse within an adapted risk assessment framework? (ii) What socio-economic models can render this integrated approach sustainable? (iii) What treatment systems and irrigation technology can be used to support these ideas and with what information? (iv) What changes in the regulations are needed?.