The radical S-Adenosylmethionine (SAM) superfamily of enzymes catalyzes a diverse range of reactions ranging from hydrogen abstraction to complicated multistep reactions such as insertions and rearrangements. The reactions they catalyze are utilized in a broad range of biological functions such as cofactor and natural product biosynthesis, DNA repair, tRNA modification, metalloproteinase cluster formation, lipid metabolism and post-transcriptional and post-translational modifications. Sealed topographies of the radical SAM superfamily include a CXXXCXXC (CX3CX2C) motif that binds a [Fe4S4] cluster essential for the reductive cleavage of SAM. This is a review of recent developments in my understanding of the structure and mechanisms of these enzymes that, I gained through the research experience at Broderick’s group at Montana State University. I am currently affiliated with Mayo Clinic’s Physiology and Biomedical Engineering department as a predoctoral student.