ConspectusPer- and polyfluoroalkyl substances (PFAS) stand for thousands of fully/highly fluorinated aliphatic chemicals, which have been widely manufactured and used in consumer products. Due to easy deprotonation of headgroups and high strength of C-F bonds in their molecules, PFAS are water-soluble and extremely stable in our environment. Significant accumulation of PFAS in water bodies started as early as the beginning of their production in the late 1940s. Recent studies confirmed the occurrence and accumulation of PFAS in all human tissues as well as their harmful health effects. Upon environmental regulations and health advisories, the PFAS industry quickly shifted to short-chain PFAS, e.g., hexafluoropropylene oxide dimer acid and its ammonium salt (GenX), to replace traditional long-chain PFAS. According to the recent fact sheet by the U.S. Environmental Protection Agency (EPA) in October 2021, however, GenX turned out to be more toxic than people originally thought and has shown health effects on liver, kidney, immune system, and so forth upon animal tests. On June 15, 2022, the EPA released the final health advisory for GenX, which is just 10 ppt. Thus, there is an urgent need of novel adsorbents for highly effective GenX remediation from water.Until now, there have been just a few reports on the remediation of GenX from water despite its popular use. In this Account, we reviewed current technology on PFAS remediation and illustrated our research on how to use polyacrylonitrile (PAN), a common and economic polymer for water filtration, in the form of nanofibrous membrane with handy chemical surface modification to develop innovative adsorbent/filter material for effective and scalable GenX remediation from water at the largest HBCU in the nation together with opportunities and challenges that are associated with this research. For the first time, we compared the GenX removal capability of electrospun PAN (ESPAN) nanofibrous membrane and amidoxime surface-functionalized ESPAN (ASFPAN) nanofibrous membrane. By modifying the surface of ESPAN nanofibrous membrane and introducing amidoxime functional group, the maximum GenX removal capacity (weight-normalized GenX removal) was almost doubled and reached ∼0.6 mmol/g at pH 4, which is higher than or comparable to that of most reported adsorbents for GenX removal. Hydrophobic interaction and dipole-dipole interaction could be the GenX adsorption mechanism on the ESPAN nanofibrous membrane while surface hydrophilicity and electrostatic interaction play major roles in GenX adsorption on the ASFPAN nanofibrous membrane. Our research shed light on understanding the GenX adsorption mechanism and developing new adsorbent/filter materials for practical short-chain PFAS remediation from water.