Human beings and wild organisms are exposed daily to a broad range of environmental stressors. Among them are the persistent organic pollutants that can trigger adverse effects on these organisms due to their toxicity properties. There is evidence that metabolomics can be used to identify biomarkers of effect by altering the profiles of endogenous metabolites in biological fluids or tissues. This approach is relatively new and has been used in vitro studies mainly. Therefore, this review addresses those that have used metabolomics as a key tool to identify metabolites associated with environmental exposure to POPs in wildlife and human populations and that can be used as biomarkers of effect. The published results suggest that the metabolic pathways that produce energy, fatty acids, and amino acids are commonly affected by POPs. Furthermore, these pathways can be promoters of additional effects. In the future, metabolomics combined with other omics will improve understanding of the origin, development, and progression of the effects caused by environmental exposure.