Procedures for environmental risk assessment for pesticides are under continuous development and subject to debate, especially at higher tier levels. Spatiotemporal dynamics of both pesticide exposure and effects at the landscape scale are largely ignored, which is a major flaw of the current risk assessment system. Furthermore, concrete guidance on risk assessment at landscape scales in the regulatory context is lacking. In this regard, we present an integrated modular simulation model system that includes spatiotemporally explicit simulation of pesticide application, fate, and effects on aquatic organisms. As a case study, the landscape model was applied to the Rummen, a river catchment in Belgium with a high density of pome fruit orchards. The application of a pyrethroid to pome fruit and the corresponding drift deposition on surface water and fate dynamics were simulated. Risk to aquatic organisms was quantified using a toxicokinetic/toxicodynamic model for individual survival at different levels of spatial aggregation, ranging from the catchment scale to individual stream segments. Although the derivation of landscape-scale risk assessment end points from model outputs is straightforward, a dialogue within the community, building on concrete examples as provided by this case study, is urgently needed in order to decide on the appropriate end points and on the definition of representative landscape scenarios for use in risk assessment.