Biodegradation is simply the metabolism of anthropogenic, or otherwise unwanted, chemicals in our environment, typically by microorganisms. The metabolism of compounds commonly found in living things is limited to several thousand metabolites whereas ∼100 million chemical substances have been devised by chemical synthesis, and ∼100 000 are used commercially. Since most of those compounds are not natively found in living things, and some are toxic or carcinogenic, the question arises as to whether there is some organism somewhere with the enzymes that can biodegrade them. Repeatedly, anthropogenic chemicals have been denoted 'non-biodegradable,' only to find they are reactive with one or more enzyme(s). Enzyme reactivity has been organized into categories of functional group transformations. The discovery of new functional group transformations has continually expanded our knowledge of enzymes and biodegradation. This expansion of new-chemical biodegradation is driven by the evolution and spread of newly evolved enzymes. This review describes the biodegradation of widespread commercial chemicals with a focus on four classes: polyaromatic, polychlorinated, polyfluorinated, and polymeric compounds. Polyaromatic hydrocarbons include some of the most carcinogenic compounds known. Polychlorinated compounds include polychlorinated biphenyls (PCBs) and many pesticides of the twentieth century. Polyfluorinated compounds are a major focus of bioremediation efforts today. Polymers are clogging landfills, killing aquatic species in the oceans and increasingly found in our bodies. All of these classes of compounds, each thought at one time to be non-biodegradable, have been shown to react with natural enzymes. The known limits of enzyme catalysis, and hence biodegradation, are continuing to expand.