Though expressed in relatively few neurons in insect nervous systems, pigment-dispersing factor (PDF) plays many roles in the control of behavior and physiology. PDF's role in circadian timekeeping is its best-understood function and the focus of this review. Here we recount the isolation and characterization of insect PDFs, review the evidence that PDF acts as a circadian clock output factor, and discuss emerging models of how PDF functions within circadian clock neuron network of Drosophila, the species in which this peptide's circadian roles are best understood.