The Stockholm Convention on Persistent Organic Pollutants (POPs) recognized that POPs resist degradation, undergo long-range transport, and accumulate in remote ecosystems. The Stockholm Convention also acknowledged that indigenous communities, particularly in the Arctic, were at risk because of the biomagnification of POPs and contamination of their traditional foods. This recognition was largely based on environmental monitoring data and demonstrates the need to have adequate guidance on data collection and use. Although long-range transport, persistence, and bioaccumulation models are important for screening potential POPs and for assessing human exposure, environmental measurement data are needed to confirm predictions. Indeed the Stockholm Convention (Annex E) requires monitoring data for assessing “exposure in local areas and, in particular, as a result of long-range environmental transport.” However, there is relatively little guidance available on the most appropriate environmental measurement approaches, particularly for new candidate POPs, and on how to create a weight of evidence based on such data. We provide guidance on how to assess existing data that have been generated by monitoring programs and individual studies on the exposure of top predators and humans to candidate or potential POPs, as well as considerations for collecting new additional data. Our overall recommendation for assessing exposure in humans and top predators is to use or obtain direct measurements of the compound of concern from a significantly and uniquely exposed population (indigenous populations, remote populations), as well as data demonstrating biomagnification within food webs and time trends if possible. These data must be from the appropriate sample matrix type, collected and analyzed using accepted methodologies, reviewed for quality assurance, and interpreted correctly in order to be used to assess exposure.