Pigment-dispersing factor (PDF) neuropeptide is an important neurochemical that carries circadian timing information originating from the central oscillator in Drosophila. Several core-clock factors function as upstream pdf regulators; the dClock and cycle genes control pdf transcription, whereas the period and timeless genes regulate post-translational processes of PDF via unknown mechanisms. For a downstream neural path, PDF most likely acts as a local modulator, which binds to its receptors that are possibly linked to Ras/MAPK signaling pathways. PDF receptor-containing cells seem to localize in the vicinity of nerve terminals from pace-making neurons. Although PDF is likely to be a principal clock-output factor, our recent evidence predicts the presence of other neuropeptides with rhythm-relevant functions. Furthermore, recent microarray screens have identified numerous potential clock-controlled genes, suggesting that diverse physiological processes might be affected by the biological clock system.