In the early days, radical enzyme reactions that use S-adenosylmethionine (SAM) coordinated to an Fe-S cluster, which Perry Frey described as a "poor man's coenzyme B12," were believed to be relatively rare chemical curiosities. Today, bioinformatics analyses have revealed the wide prevalence and sheer numbers of radical SAM enzymes, conferring superfamily status. In this thematic minireview series, the JBC presents six articles on radical SAM enzymes that accomplish wide-ranging chemical transformations. We learn that despite the diversity of the reactions catalyzed, family members share some common structural and mechanistic themes. Still in its infancy, continued explorations promise to be fertile grounds for discoveries that will undoubtedly further broaden our understanding of the catalytic repertoire and deepen our understanding of the chemical strategies used by radical SAM enzymes.