Recent gene discovery approaches have led to a new era in our understanding of the molecular basis of circadian oscillators in animals. A conserved set of genes in Drosophila and mammals (Clock, Bmal1, Period, and Timeless) provide a molecular framework for the circadian mechanism. These genes define a transcription-translation-based negative autoregulatory feedback loop that comprises the core elements generating circadian rhythmicity. This circadian core provides a focal point for understanding how circadian rhythms arise, how environmental inputs entrain the oscillatory system, and how the circadian system regulates its outputs. The addition of molecular genetic approaches to the existing physiological understanding of the mammalian circadian system provides new opportunities for understanding this basic life process.