The genomics era has presented scientists with an overwhelming amount of sequence information that encodes for a continuously expanding array of metabolic pathways and regulatory networks. In order to unravel this elaborate maze, effective approaches need to be pioneered, and cyclic peptides represent an exciting new tool that can aid this challenging task. There are considerable benefits to cyclic peptides including enhanced protein binding affinity and metabolic stability, but perhaps most important is the ability to biologically synthesize them using intein chemistry. This capacity for genetic encoding allows biologists access to diverse, intracellular small-molecule libraries that can be tailored for numerous chemical genetics approaches. An increasing number of molecular strategies are being developed to aid in the implementation of cyclic peptides in forward and reverse genetics experiments, which will provide researchers with a powerful toolbox to complement existing genomic methodologies.