The risks resulting from the use, release and effects of chemicals to the environment are addressed in a plethora of EU-level Directives and regulatory strategies, each with specific (chemical) targets and protection aims. There is, however, concern that such a fragmented regulatory approach does not adequately capture all threats of chemicals to biodiversity and ecosystem services. To protect genetic and functional biodiversity from pollution impacts, a paradigm shift is needed. This transformation should move beyond the current fragmented Environmental Risk Assessment (ERA) performed in specific regulatory silos, e.g., Plant Protection Products (PPPs) regulation for pesticides, REACH for industrial chemicals and Biocidal Product Regulation, towards a harmonised and systems-based ERA, applicable to all chemicals, species and land uses. To make this advance, it is essential to rationalise the current silo-based Protection Goals into high-level systems-based Protection Goals and to operationalise the use of a robust and broadly systems-based ERA within different ERA frameworks.