With the increasing utilization of high-throughput screening for lead identification in drug discovery, the need for easily constructed and diverse libraries which cover significant chemical space is greater than ever. Cyclic peptides address this need; they combine the advantageous properties of peptides (ease of production, high diversity, high potential specificity) with increased resistance to proteolysis and often increased biological activity (due to conformational locking). There are a number of techniques for the generation and screening of cyclic peptide libraries. As drug discovery moves toward tackling challenging targets, such as protein-protein interactions, cyclic peptide libraries are expected to continue producing hits where small molecule libraries may be stymied. However, it is important to design robust systems for the generation and screening of these large libraries, and to be able to make sense of structure-activity relationships in these highly variable scaffolds. There are a plethora of possible modifications that can be made to cyclic peptides, which is both a weakness and a strength of these scaffolds; high variability will allow more precise tuning of leads to targets, but exploring the whole range of modifications may become an overwhelming challenge.