Per- and polyfluoroalkyl substances (PFASs) have been under intense investigation by the scientific community due to their persistence in the environment and potentially hazardous effects on living organisms. In order to tackle the presence of these compounds in water, to date, the research has been strongly focused on the evaluation of the effectiveness of different types of technologies. Considering the extreme complexity of the matter of PFASs and our relatively low knowledge in this topic, the following question arises: is the “chemical only” approach that is followed for evaluating the effectiveness of technologies for PFAS removal from water reliable enough? In this work, some limitations of the present approach are discussed, highlighting the reasons why it cannot be considered a reliable tool to correctly estimate the effectiveness of technology when referring to emerging compounds such as PFASs. Bioassays can play a key role in moving towards an integrated bio-chemical evaluation (chemical analysis and ecotoxicological evaluation), which is strongly encouraged. This represents the only way to completely characterize a water matrix and fully evaluate the impact of technologies when dealing with micropollutants in water, such as PFASs. Future research should focus on defining an optimal battery of bioassays that specifically fit to best represent changes in water quality in terms of short- and long-term impacts on living organisms.