Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are ubiquitous synthetic chemicals with no known effect on human cancer development. This article systematically and critically reviews the epidemiologic evidence regarding the association between PFOA and PFOS exposure and cancer risk in humans. Eighteen epidemiologic studies - eight of PFOA, four of PFOS, and six of both PFOA and PFOS - have estimated associations of exposure to these chemicals with cancer incidence or mortality, with studies equally divided between occupational and nonoccupational settings. Although some statistically significant positive associations have been reported, for example, with cancers of the prostate, kidney, testis, and thyroid, the majority of relative risk estimates for both PFOA and PFOS have been between 0.5 and 2.0 (with 95% confidence intervals including 1.0), inconsistently detected across studies, counterbalanced by negative associations, not indicative of a monotonic exposure-response relationship, and not coherent with toxicological evidence in animals, in which the primary target organs are the liver, testis (Leydig cells), and pancreas (acinar cells). Many positive associations with PFOA exposure were detected in community settings without occupational exposure and were not supported by results in exposed workers. Given that occupational exposure to PFOA and PFOS is one to two orders of magnitude higher than environmental exposure, the discrepant positive findings are likely due to chance, confounding, and/or bias. Taken together, the epidemiologic evidence does not support the hypothesis of a causal association between PFOA or PFOS exposure and cancer in humans.