This paper summarises the results of the Sphere+ Project (Substitution Projects for Health and Environment, Lessons from Results and Experiences) and in particular the outcomes of FEEM’s contribution in the field of substituting hazardous molecules used to control weeds to preserve the quality of water resources. The story of the study case started in Italy, in the mid 80’s, with the introduction of the EC Directive 80/778 concerning drinking water. The acceptable limits for pesticide concentrations were so low that most of the groundwater sources for northern Italian towns’ aqueducts became unsuitable for human consumption, quite often because of high concentrations of the herbicide Atrazine (commonly used for maize cultivation). This paper examines the story of the substitution of Atrazine with alternatives that have a lower environmental impact, focussing in particular on the comparison between end users’ and institutional perspectives, policy implications, the relationship between communication and political strategies and the research sector.