The genome sequencing efforts of the past 20 years have revealed that ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a large class of peptide natural products. These molecules are produced in all three domains of life, their biosynthetic genes are ubiquitous in the currently sequenced genomes, and their structural diversity is vast. Furthermore, they are increasingly recognized for their involvement in fighting or causing human disease. This presentation will discuss the use of genome mining and synthetic biology for the discovery of new cyclic RiPPs via an automated platform and the unusual chemistry involved in their biosynthesis.