The extent to which perfluorooctanesulfonate precursors (PreFOS) play a role in human or environmental exposure to perfluorooctanesulfonate (PFOS) is not well characterized. The diversity of manufactured PreFOS and its degradation products (e.g. C8F17SO2R and C8F17SO2NR′R′′, where R is H or F, and R′ and R′′ are various) has made it difficult to track their fate. Temporal trends of PFOS in both humans and wildlife are discrepant, thus it is difficult to predict future exposure, and hypotheses about the role of PreFOS have been raised. Although abiotic degradation of commercially important PreFOS materials requires further research, current data suggest that the yield of PFOS is negligible or minor. On the other hand, in vivo biotransformation of PreFOS yields PFOS as the major metabolite, and >32% yields have been observed. In Canadians, exposure to PreFOS was equivalent or greater than direct PFOS exposure prior to 2002. In most ocean water, PFOS is dominant to PreFOS, but in the oceans east of Greenland there may be more PreFOS than PFOS, consistent with the fact that whales and humans in this region also show evidence of substantial PreFOS exposure. Quantitative assessments of PFOS body-burdens coming from PreFOS are complicated by the fact that PreFOS partitions to the cellular fraction of blood, thus biomonitoring in serum under predicts PreFOS relative to PFOS. Many unknowns exist that prevent accurate modelling, thus analytical methods that can distinguish directly manufactured PFOS, from PFOS that has been biotransformed from PreFOS, should be applied in future human and environmental monitoring. Two new source tracking principles are presented and applied to human serum.