Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) comprise a class of per- and poly-fluorinated compounds that have been detected in the environment as well as in humans. The aim of this review is to summarize several monitoring studies in Japan and characterize the toxicokinetics of these compounds. We found that the levels of contamination by these compounds had unique patterns in Japan. The levels of PFOA in serum from inhabitants of the Kansai region were higher than those of other regions. The PFOA levels in air and water samples from the Kansai region were also relatively high. The estimated intakes from these routes partly explain the differences in the serum levels. The toxicokinetics of these compounds have been investigated. Serum samples from male participants had significantly higher geometric means for PFOS and PFOA compared to samples from female participants. This sex-related difference was partly simulated by menstrual blood loss. There are large interspecies differences in the excretion pathways of these compounds. The serum clearances of PFOA via urine were 300–1,000-fold lower in humans than in Wistar rats and Japanese macaques. On the other hand, the biliary excretion of these compounds was comparable in rats and humans, and the long half-lives in humans may be attributable to the low levels of urinary excretion and high biliary reabsorption rates. These findings suggest that qualitative differences in the excretion routes exist between humans and other species. For risk assessment of these compounds, further information regarding sources of exposure and their toxicokinetics is needed.