The water system provides many services to society; industries, municipalities and agriculture all withdraw, use and return water and demand a water quality fit for the intended purposes. Both global production of chemicals and global water withdrawal grow faster than human population. This implies increased chemical threats to water, and creates a strong driver for mitigation to protect human health, ecosystem integrity and ecosystem services. Here we connect the perspectives of the water cycle and the chemical life cycle and review possible mitigation options. We categorize mitigation options in various stages of the chemicals' life cycle, taking various sectors and environmental pathways into account. More technologically oriented versus other types of mitigation options are discerned, and their relevance on spatial and temporal scale is discussed. We review various water treatment techniques in relation to physical–chemical properties of chemicals. Finally we discuss how a mitigation database can be used to assess the effectiveness of interventions, by coupling them to regional or global hydrological models. A solution-focused and systems-oriented perspective combined with a mitigation database offers a common perspective amongst actors on the effects for water quality of possible mitigation options throughout the chemical's life cycle, in various sectors and at various places in the water system. This can stimulate coherent implementation of effective mitigation options, cross-sectoral learning and further innovations to improve water quality.