Among aspects of agricultural intensification that have been criticized for negative impacts on biodiversity (1, 2), pesticides have been linked to declines in insects, birds, and biodiversity in aquatic systems (3–5). If pesticide use is to blame, even partially, then this raises questions both about pesticide use and the regulatory procedures that are used to protect the environment (4). Environmental risk assessment (ERA) of pesticides does not account for many stressors that have intensified in recent years, such as climate change, habitat destruction, and increasing landscape homogeneity, the combination of which can aggravate effects of pesticides in nature. We describe how several assumptions underlying ERA may not hold in modern intensive agricultural landscapes, and the interaction among assumption violations may account for observed declines in biodiversity. Using European contexts to exemplify these global concerns, we review how regulatory ERA for pesticides has fallen out of step with scientific knowledge (4) and societal demands for sustainable food production and suggest systematic and recently feasible changes for regulation.