The increasing health risks posed by per- and polyfluoroalkyl substances (PFASs) in the environment highlight the importance of implementing effective removal techniques. Conventional wastewater treatment processes are inadequate for removing persistent organic pollutants. Recent studies have increasingly demonstrated that metal-organic frameworks (MOFs) are capable of removing PFASs from water through adsorption techniques. However, there is still constructive discussion on the potential of MOFs in adsorbing and removing PFASs for large-scale engineering applications. This review systematically investigates the use of MOFs as adsorbents for the removal of PFAS in water treatment. This primarily involved a comprehensive analysis of existing literature to understand the adsorption mechanisms of MOFs and to identify factors that enhance their efficiency in removing PFASs. We also explore the critical aspects of regeneration and stability of MOFs, assessing their reusability and long-term performance, which are essential for large-scale water treatment applications. Finally, our study highlights the challenges of removing PFASs using MOFs. Especially, the efficient removal of short-chain PFASs with hydrophilicity is a major challenge, while medium- to long-chain PFASs are frequently susceptible to being captured from water by MOFs through multiple synergistic effects. The ion-exchange force may be the key to solving this difficulty, but its susceptibility to ion interference in water needs to be addressed in practical applications. We hope that this review can provide valuable insights into the effective removal and adsorption mechanisms of PFASs as well as advance the sustainable utilization of MOFs in the field of water treatment, thereby presenting a novel perspective.