With an increased interest in the use of peptides as therapeutics comes the need for strategies to allow for the discovery of novel hit candidates, in high-throughput manners, from highly complex peptide libraries. Early development of peptide therapeutics arose from the deployment of natural peptides and subsequent modification to enhance medicinal properties. Here, the implementation of synthetic peptide libraries of low complexity was sufficient, but these low-diversity starting points are an obvious limitation to the discovery of novel peptides. This limitation is compounded by the almost unarguable desire to explore unnatural amino acid chemical space, moving away from the reliance upon natural peptides.