Ribosomally synthesized and post-translationally modified peptides (RiPPs) are known for their macrocyclic structures, which impart unique biological activity. One rapidly emerging subclass of RiPP natural products contains macrocyclic C− C cross-links between two amino acid side chains. These linkages, often biosynthetically formed by a single rSAM or P450 enzyme, introduce significant structural and synthetic complexity to the molecules. While nature utilizes elegant mechanisms to produce C− C cross-linked RiPPs, synthetic tools are only able to access a portion of these biologically relevant natural products. This review provides an overview of the structures in this subclass as well as a discussion on their chemical syntheses.