Enhanced sensitivity of analytical chemistry methods has enabled the detection of low-levels of pharmaceuticals in the environment, resulting in questions about the safety of surface waters used for drinking supplies. Human health risk assessments were performed to evaluate the risks from residues of atomoxetine, duloxetine, and olanzapine, which might be found in surface waters. Preclinical safety studies and human clinical data were used to determine an acceptable daily intake (ADI) for each compound: atomoxetine, 1.4 microg/kg/day; duloxetine, 1.8 microg/kg/day; and olanzapine, 1.4 microg/kg/day. The calculated predicted no-effect concentrations (PNECs) for children were 25.7, 19.1, and 35.9 microg/L for atomoxetine, duloxetine, and olanzapine, respectively. Estimated exposure concentrations determined using United States Food and Drug Administration guidelines and predicted exposure concentrations from the PhATE model were compared with each PNEC to determine margins of safety, which ranged from 147 to 642. Based on currently available data used in this assessment, no appreciable human health risks exist from exposure to the highest 99th percentile of predicted residue levels of atomoxetine, duloxetine or olanzapine in surface waters under low-flow conditions.