Due to the challenges with detection trace organic chemicals (TOrCs) in wastewater, using traditional approaches like identifying and screening unknown chemicals and their persistence through wastewater treatment processes is an important area of research. Non-targeted analytical (NTA) approaches can screen for hundreds or thousands of distinct chemicals and make it possible to identify unexpected chemicals and transformation products that targeted approaches may overlook. This project evaluated the persistence, removal, and transformation of TOrCs through 1.) aerobic and anaerobic membrane bioreactor systems treating primarily domestic wastewater at the lab-scale; 2.) conventional activated sludge systems treating wastewater from U.S. and South African municipalities at the centralized scale; and 3.) a decentralized anaerobic treatment system with constructed wetlands treating domestic wastewater at the neighborhood scale. Additional funding for this work was provided by the National Science Foundation.