Pharmaceuticals are important contaminants of concern in aquatic environments and are now detected in surface waters worldwide. However, the ecological impacts of PPCPs as well as their bioaccumulation potential (via trophic transfer) are not well understood. We sampled 6 streams across an urban-rural gradient seasonally for 2 years. Using a conceptual model based on two chemical traits, water solubility and metabolic transformation rate, we were able to predict which pharmaceutical compounds had the greatest potential to bioaccumulate. To test bioaccumulation predictions we collected freshwater insects and riparian spiders and analyzed their pharmaceutical concentration. PPCPs were detected in benthic freshwater insects and in riparian spider tissue; suggesting that some PPCPs do have the potential to bioaccumulate. Further, we then quantified the standing stock of PPCPs occurring in benthic freshwater insects (PPCPs/g insect/m2) in order to calculate the flux of PPCPs to higher consumers via insect consumption. These findings raise important concerns regarding the fate of PPCPs in stream food webs and potential exposure risks to stream and riparian predators feeding on PPCP laden insects.