Today’s agriculture heavily relies on pesticides to manage diverse pests and maximise crop yields. Despite elaborate regulation of pesticide use based on a complex environmental risk assessment (ERA) scheme, the widespread use of these biologically active compounds has been shown to be a threat to the environment. For surface waters, pesticide exposure has been observed to exceed safe concentration levels and negatively impact stream ecology leading to the question whether current ERA schemes ensure a sustainable use of pesticides. To answer this, the large-scale “Kleingewässer-Monitoring” (KgM) assessed the occurrence of pesticides and related effects in 124 streams throughout Germany, Central Europe, in 2018 and 2019. Based on five scientific publications originating from the KgM, this thesis evaluated pesticide exposure in streams, ecological effects and the regulatory implications. More than 1,000 water samples were analysed for over 100 pesticide analytes to characterise occurrence patterns (publication 1). Measured concentrations and effects were used to validate the exposure and effect concentrations predicted in the ERA (publication 2). By jointly analysing real-world pesticide application data and measured pesticide mixtures in streams, the disregard of environmental pesticide mixtures in the ERA was evaluated (publication 3). The toxic potential of mixtures in stream water was additionally investigated using suspect screening for 395 chemicals and a battery of in-vitro bioassays (publication 4). Finally, the results from the KgM stream monitoring were used to assess the capability to identify pesticide risks in governmental monitoring programmes (publication 5). The results of this thesis reveal the widespread occurrence of pesticides in non-target stream ecosystems. The water samples contained a variety of pesticides occurring in complex mixtures predominantly in short-term peaks after rainfall events (publications 1 & 4). Respective pesticide concentration maxima were linked to declines in vulnerable invertebrate species and exceeded regulatory acceptable concentrations in about 80% of agricultural streams, while these thresholds were still estimated partly insufficient to protect the invertebrate community (publication 2). The co-occurrence of pesticides in streams led to a risk underestimated in the single substance-oriented ERA by a factor of about 3.2 in realistic worst-case scenarios, which is further exacerbated by a high frequency at which non-target organism are exposed to pesticides (publication 3). Stream water samples taken after rainfall caused distinct effects in bioassays which were only explainable to a minor extent by the many analytes, indicating the relevance of unknown chemical or biological mixture components (publication 4). Finally, the regulatory monitoring of surface waters under the Water Framework Directive (WFD) was found to significantly underestimate pesticide risks, as about three quarters of critical pesticides and more than half of streams at risk were overlooked (publication 5). Essentially, this thesis involves a new level of validation of the ERA of pesticides in aquatic ecosystems by assessing pesticide occurrence and environmental impacts at a scale so far unique. The overall results demonstrate that the current agricultural use of pesticides leads to significant impacts on stream ecology that go beyond the level tolerated under the ERA. This thesis identified the underestimation of pesticide exposure, the potential insufficiency of regulatory thresholds and the general inertia of the authorisation process as the main causes why the ERA fails to meet its objectives. To achieve a sustainable use of pesticides, the thesis proposes substantial refinements of the ERA. Adequate monitoring programmes such as the KgM, which go beyond current government monitoring efforts, will continue to be needed to keep pesticide regulators constantly informed of the validity of their prospective ERA, which will always be subject to uncertainty.