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Numerous studies have reported the presence of several endocrine disrupting compounds (EDC) and pharmaceuticals and personal care products (PPCP) in wastewater effluents and consequently in natural water sources which serve as source water for drinking water utilities. However it is still unclear as to which of these compounds are important and need to be monitored. This paper proposes a new approach to identify indicators or surrogates to monitor these compounds in a watershed based on intensive sampling, analytical methods and statistical analysis. The watershed-level protocol involves identifying common patterns of occurrence in these trace chemicals and proposes indicators based on results of statistical analyses such as correlation, cluster and principal component analysis. The application of the indicators to predict concentration levels of other compounds is evaluated by developing regression models and determining significance of the models. Sampling was performed in the Assabet River in Massachusetts and 26 trace compounds and 3 tracers were targeted in the analysis. It was found that gadolinium served as an indicator for 14 other compounds. The application of this protocol will help drinking water utilities and regulators alike to more effectively utilize their allocated resources.