Why is the biodegradation of polyfluorinated compounds so rare?

Thousands of heavily fluorinated chemicals are found in the environment, impact human and ecosystem health, and are relatively resistant to biological and chemical degradation. Their persistence in the environment is due to the inability of most microorganisms to biodegrade them. Only a very few examples of polyfluorinated compound biodegradation are known, and the reported rates are very low. This has been mostly attributed to the low chemical reactivity of the C-F bond. This Perspective goes beyond that explanation to highlight microbiological reasons why polyfluorinated compounds resist metabolism. The evolutionary and physiological impediments must be appreciated to better find, study, and harness microbes that degrade polyfluorinated compounds.