Increasing studies are examining per- and polyfluoroalkyl substances (PFAS) induced toxicity and resulting health outcomes, including epigenetic modifications (e.g., DNA methylation, histone modification, microRNA expression). We critically reviewed current evidence from human epidemiological, in vitro, and animal studies, including mammalian and aquatic model organisms. Epidemiological studies identified the associations between perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) exposure and epigenetic changes in both adult populations and birth cohorts. For in vitro studies, various cell types including neuroblasts, preadipocytes, and hepatocytes have been employed to understand epigenetic effects of PFAS. In studies with animal models, effects of early life exposure to PFAS have been examined using rodent models, and aquatic models (e.g., zebrafish) have been more frequently used in recent years. Several studies highlighted oxidative stress as a key mediator between epigenetic modification and health effects. Collectively, previous research clearly suggest involvement of epigenetic mechanisms in PFAS induced toxicity, though these efforts have primarily focused on specific PFASs (i.e. mainly PFOS and PFOA) or endpoints (i.e. cancer). Additional studies are necessary to define specific linkages among epigenetic mechanisms and related biomarkers or phenotypical changes. In addition, future research is also needed for understudied PFAS and complex mixtures. Studies of epigenetic effects elicited by individual PFAS and mixtures are needed within an adverse outcome pathways framework, which will advance an understanding of PFAS risks to public health and the environment, and support efforts to design less hazardous chemicals.