Despite regulatory frameworks designed to prevent environmental damage, pesticide use is still linked to declines in insects, birds and aquatic species, an outcome that raises questions about the efficacy of current regulatory procedures. In a Policy Forum, Christopher Topping and colleagues argue that this discordance between pesticide policy and their observed impacts stems from aging Environmental Risk Assessment (ERA) regulations, which have fallen out of line with environmental policy and with the science behind our current ecological reality. In both the European Union and the United States, basic ERA guidelines are decades old and based on assumptions that misrepresent the dynamic ecological systems in modern agricultural landscapes. For example, ERA typically does not account for the fact that climate change, habitat loss and large-scale landscape homogenization can exacerbate the adverse impacts of pesticides. According to the authors, a radical overhaul of ERA is required in order to implement a regulatory framework that delivers adequate environmental protection. Topping et al. propose a more holistic, integrated systems-based approach to pesticide regulation, which would be better able to align multiple agricultural practices with dynamic agroecological factors in pesticide regulation. While this radical change would require challenging changes to administrative structures and a reevaluation of current protections regulations, the fundamental science, technology and data required to support such a system are already available, the authors say.