The risks associated with pesticides in small streams remain poorly characterized. The challenges reside in understanding the complexities of (1) the highly dynamic concentration profiles of (2) several hundred active substances with (3) differing seasonality. The present study addressed these three challenges simultaneously. Five small streams in catchments under intensive agricultural land use were sampled using half-day composite samples from March to August 2015. Of 213 active substances quantified using liquid chromatography–high resolution mass spectrometry, a total of 128 was detected at least at one of the sites. Ecotoxicological acute and/or chronic quality criteria were exceeded for a total of 32 different active substances. The evaluation of risks over time revealed the necessity to evaluate the sequences of different active substances that are imposed on aquatic organisms. In contrast, a substance-specific perspective provides only a very limited assessment. Scenarios for reduction of either temporal resolution, number of substances or seasonal coverage were defined. It could be shown that risks can be underestimated by more than a factor of 10 in vulnerable catchments and that an increased temporal resolution is essential to cover acute risks but that a focused selection of substances is a possibility to reduce expenditures.