Background Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are two fluorinated compounds widely used in industry because of their useful chemical characteristics. They were identified as endocrine disruptors due to their ability to interfere with thyroid function. The resistance of PFOA and PFOS to environmental degradation, their bio-accumulation in food chains, and their long half-life raised concern in the scientific community, and several studies were performed with the aim to establish the real dangerousness of these compounds for the human health. Purpose The present review will focus on the effects of PFOA and PFOS on the thyroid gland taking into account in vitro experiments, animal studies, and human data. PFOS and PFOA reduce the circulating levels of thyroid hormones in diet-exposed animals, mainly by increasing their metabolic clearance rate. Conclusions An accumulation of PFOS and PFOA was documented in thyroid cells, and a cytotoxic effect was observed after exposure to extremely high concentrations of these compounds. In environmentally exposed communities and in the general population, the most consistent effect of exposure to PFOA, and to a less extent to PFOS, is the occurrence of hypothyroidism. Women and children appear to be more at risk of developing mild thyroid failure. Pregnant women with circulating thyroid antibodies might be at risk of developing subclinical hypothyroidism, mainly when exposed at high doses of PFOS. The relative risks for thyroid cancer in people exposed to PFOA and PFOS were low and based on a few cases. Moreover, there was no consistent finding across all or even most studies.