There has been growing concern about the detection and potential toxicological significance of pharmaceutically active compounds in sewage impacted surface waters and sediments. The concentrations of municipal wastewater-derived chemicals in the highly urbanized NY/NJ Harbor Complex are among the highest reported. In this paper we review some of the progress we have made in LC-MS-based detection of many classes of pharmaceutically active compounds, as well as work on understanding their fate in estuarine waters and sediments. Those studies have allowed us to assess the potential uses of wastewater contaminants as tracers of contaminant sources and transport in seawater (e.g., persistent and soluble pharmaceuticals)and in sediments (persistent and strongly sorbed quaternary amine disinfectants). These tracers have allowed us to further assess the sources and in-situ transformations of a wider range of contaminants, including natural estrogens and estrogenic detergent metabolites.