A video recording of this presentation can be found here. Water that is safe and clean is essential for all life. A concerning, worldwide trend is that sources of drinking water have become increasingly contaminated with substances considered persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM). Well known examples include melamine, 1,4-dioxane, trifluoroacetate and several PFAS. PMT/vPvM substances are those which do not breakdown easily in the environment (persistent), are transported relatively rapidly through soil and groundwater (mobile) and are in some cases toxic. They are associated with widespread, negative effects on the environment and human health. Advanced water treatment methods, like ozonolysis or activated carbon filtration, are often ineffective. This has led to several civil and legal disputes regarding who should pay for expensive remediation and clean-up costs. Industry, regulators, academia, and the water sector are now taking action to reduce pollution from PMT/vPvM substances. A focal point of this action is the European Union’s Green Deal, particularly its Chemicals Strategy for Sustainability towards a Toxic Free Environment and its Zero Pollution ambition. Building off an initiative by the German Environment Agency (UBA), new hazard classes for PMT/vPvM substances are currently being implemented in two of the main European chemical regulations, CLP and REACH. This will support industry and regulators to replace them with safer and more sustainable alternatives. Also, a planned review of the European Union’s environmental laws aims to reduce pollution by 2050 “to levels no longer considered harmful to health and natural ecosystems and that respect [planetary boundaries]“. Achieving this will require advancement and collaboration to address several scientific, technological, regulatory and social-scientific needs regarding PMT/vPvM substances. These needs include the following that will be highlighted in this keynote. Science needs: i) obtaining good quality persistency assessments using fewer resources; ii) advancing research on the mobility of charged organic compounds; iii) understanding the (eco)toxicity endpoints from long term exposure to groups of substances, as well as planetary boundary considerations for accumulating persistent substances; iv) developing sustainability assessments over the whole life cycle of chemicals including end-of-life water treatment; v) advancing risk assessment tools that consider wastewater recycling, bank filtration, drought and multiple-stressors Technology needs: vi) addressing the costs and limitations of monitoring highly mobile substances, particularly transformation products and substance mixtures; vii) developing sustainable, cost-effective strategies to manage or remediate existing PMT/vPvM substance contamination; Regulatory needs: viii) ensuring a harmonized approach across all EU legislation regarding PMT/vPvM substances; ix) developing the essential use concept and alternative assessment tools for PMT/vPvM substances, alongside incentives for industry to pursue safe and sustainable alternatives; Social-science needs: x) developing mental models to understand the social factors that would lead to less PMT/vPvM substance pollution, xi) developing systems to coordinate industry stewardship, regional risk governance programs and stakeholder involvement to protect sources of drinking water. The keynote will present how the SETAC community can work together to address these needs to achieve the Zero Pollution ambition, ensuring safe, sustainable and clean water resources for future generations.