For a long time, it was held that free radicals are bad actors and described as reactive oxygen or nitrogen species (ROS, RNS) such as O2•−, HO•, and NO•. Redox biology is the fundamental aspect of aerobic life—being the terminal electron acceptor—they cannot avoid oxygen and its reduction. Uncontrolled reduction of O2 and its reduced species can be deleterious to biomolecules critical to life like DNA. It is now well accepted that many essential biochemical reactions also involve organic radicals. Reactions catalyzed by metalloenzymes like cytochrome P450, ribonucleotide reductase, and the adenosylcobalamin (AdoCbl or B12) enzymes employ organic radical intermediates. Generally, radical chemistry with enzymes is resorted by nature, for reactions that would be difficult or impossible to catalyze by polar mechanisms. Most often such reactions involve an H-atom (not a proton) abstraction from a recalcitrant C–H bond. The radical S-adenosylmethionine (radical SAM; rSAM) enzymes are the more recent superfamily of such enzymes with over half a million members widely spread across the tree of life. Information explosion through analysis of sequenced genomes suggests that >500,000 enzymes/proteins exploit radicals for their chemistry.