Abstract: Per- and polyfluoroalkyl substances (PFASs) with persistence, bioaccumulation, and toxicity properties have gained attention worldwide because of their potential environmental risks and adverse health effects. Recently, PFASs were proposed to be managed as a highly persistent class, and all “nonessential” uses of these chemicals should be phased out. In view of their wide application in various fields which involve huge socio-economic impacts, it is a long way to go in reaching consensus on PFASs management. Currently, meaningful actions are needed to minimize the potential exposure risk of PFASs while simultaneously fulfilling their social needs. Transformation studies could help identify transformation products with less persistent properties and low toxicity, which will provide valuable insight into designing safer fluorinated alternatives. For the first time, we propose that strengthening the study on the transformation of PFASs is an important strategy for classifying and managing fluorinated alternatives, and this will provide technical framework and support for fluorinated alternatives regulation for REACH. Proposals for investigating transformation process of PFASs including, firstly, nontargeted and high-resolution mass spectrometry technologies must be continually developed. Secondly, the transmission, accumulation, metabolism, and elimination behaviors of PFASs in different matrices should be of high concern. Lastly, the biological networks elaborating the relationship between PFASs transformation products and adverse health effects should be established.