Lawrence P. Wackett argues that the persistence of per- and polyfluorinated compounds (PFAS) in the environment is not primarily due to the strength of C–F bonds but rather due to evolutionary limitations. While C–F bonds are strong, enzymes have been found to cleave them, suggesting that the resistance of PFAS to biodegradation is more a matter of biological adaptation than chemical properties. The challenge lies in the fact that degrading PFAS requires multiple enzymatic functions that are not naturally evolved, and the toxic fluoride anion produced during degradation imposes strong negative selection against biodegradation. Despite this, recent studies show that some bacteria can degrade PFAS, indicating that evolution can adapt to these compounds. However, the energy yield from degrading PFAS is low, and the toxicity of fluoride makes it difficult for microbes to survive the process. The article emphasizes that PFAS are foreign to biology, requiring new metabolic pathways for degradation, and that their biodegradation is only possible with robust mechanisms to manage fluoride toxicity. The evolutionary adaptation of microbes to degrade PFAS is complex and requires multiple functions, making it a steep evolutionary challenge. The article concludes that the persistence of PFAS is best explained by evolutionary insufficiency rather than inherent enzyme inadequacy.Lawrence P. Wackett argues that the persistence of per- and polyfluorinated compounds (PFAS) in the environment is not primarily due to the strength of C–F bonds but rather due to evolutionary limitations. While C–F bonds are strong, enzymes have been found to cleave them, suggesting that the resistance of PFAS to biodegradation is more a matter of biological adaptation than chemical properties. The challenge lies in the fact that degrading PFAS requires multiple enzymatic functions that are not naturally evolved, and the toxic fluoride anion produced during degradation imposes strong negative selection against biodegradation. Despite this, recent studies show that some bacteria can degrade PFAS, indicating that evolution can adapt to these compounds. However, the energy yield from degrading PFAS is low, and the toxicity of fluoride makes it difficult for microbes to survive the process. The article emphasizes that PFAS are foreign to biology, requiring new metabolic pathways for degradation, and that their biodegradation is only possible with robust mechanisms to manage fluoride toxicity. The evolutionary adaptation of microbes to degrade PFAS is complex and requires multiple functions, making it a steep evolutionary challenge. The article concludes that the persistence of PFAS is best explained by evolutionary insufficiency rather than inherent enzyme inadequacy.