Wastewater reuse is currently considered globally as the most critical element of sustainable water management. Water scarcity, foreseen to aggravate, pushes for maximum utilization of non-conventional water. Although reuse is accompanied by a number of benefits, several potential drawbacks still puzzle scientists. The applied treatments fail to completely remove microcontaminants, antibiotic-resistant bacteria and/or their genes (ARB&Gs). Knowledge on the actual effects of reuse with regard to these aspects is currently not consolidated. This Action will answer critical questions through a European multidisciplinary network, structured in interactive Working Groups (WGs), to achieve: a) identification of the microbiome and mobile antibiotic resistome in treated wastewater, b) assessment of the potential for uptake/transmission of microcontaminants and ARB&Gs in crops, c) determination of effect-based bioassays required for wastewater reuse, d) identification of efficient/economically viable technologies able to meet the current challenges and, e) development of a relevant risk assessment and policy framework. The Action will establish criteria on technologies/assessment methods for wastewater treatment and suggest new effluent quality criteria to overcome current barriers and safeguard the reuse practice. The Action will have a major impact on the enhancement of sustainable wastewater reuse in light of current challenges at technological, economical and societal level.