On 8th May 2017, journal club meeting, the topic “Toxicity of perfluorooctanoic acid: Implications for health risks.” was discussed. As an emerging persistent organic pollutant (POP), perfluorooctanoate (PFOA) is one of the most abundant perfluorinated compounds (PFCs) in the environment. This molecular mechanisms and signaling pathways of PFOA-induced toxicity in animals and humans as well as their implications for health risks in humans were described. Traditional PFOA-induced signal pathways such as peroxisome proliferating receptor alpha (PPARα), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), and pregnane-X receptor (PXR) may not be important for PFOA-induced health effects on humans. Instead, pathways, including p53/mitochondrial, nuclear lipid hyperaccumulation, phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT), and tumor necrosis factor-α/nuclear factor κB (TNF-α/NF-κB) play roles for PFOA-induced health risks in humans. Both in vivo and in vitro studies are needed to better understand the PFOA-induced toxicity mechanisms as well as the associated health risk in humans.