Oxidative treatment methods are valuable tools for the microbial safety of drinking water. However, the reaction of oxidants with natural substances or anthropogenic contaminants present in the raw water can potentially lead to the formation of harmful transformation products (TPs). The present paper proposes a tiered approach for the risk evaluation of TPs formed from pesticide residues during drinking water treatment. First, the concentrations of pesticide residues in raw water used for drinking water production are evaluated (step 1). Substances with a predicted concentration in raw water above 0.1 µg/L proceed further to a reactivity assessment, examining the behavior in water treatment plants (step 2). Using information available in the scientific literature, prediction of structural elements in the TPs can be made and allow a worst-case assessment based on the Threshold of Toxicological Concern (TTC) (step 3). If concerns remain, experiments may be conducted to simulate water treatment (step 4). Because of their complexity and variability, experiments for the simulation of water treatment should focus on prioritized substances of potential concern. The test conditions should be realistic (i.e., close to EU-representative conditions in waterworks) and ozonation and chlorination should be combined with pre- and post-treatment steps, as is normally the case in European waterworks. As a first screening option, we propose to test the toxicity of the reaction mixture. If the treated water shows an enhanced toxicity, further experiments can be conducted to identify and quantify the major TPs (step 5). We propose to define major TPs as substances present at more than 10% of the initially applied test substance. For major TPs, a tiered dietary risk assessment is conducted, starting with the TTC concept, and continuing with toxicity testing of the TP, according to EFSA and ECHA and internationally agreed guidance.