In mammals, almost all aspects of physiology and behavior are under the control of the circadian clock and therefore display daily oscillations. The circadian timekeeping mechanism is composed of a central pacemaker residing in the suprachiasmatic nuclei (SCN) in the brain and subsidiary clocks in virtually all body cells. The SCN is synchronized in a daily fashion by light and in turn ensures phase coherence of subsidiary oscillators in the periphery via various humoral and neuronal signals. On the cellular level, the mammalian circadian oscillator is believed to rely on interlocked transcriptional-translational feedback loops, and rhythm generation is achieved by the precise interplay of positive and negative transcriptional elements. The positive limb is comprised of the transcription factors BMAL1 and CLOCK. BMAL1/CLOCK heterodimers associate with regulatory sequences in the Period (Per) and Cryptochrome (Cry) genes, which constitute the negative limb, and activate their expression. After accumulating in the cytoplasm, PERs and CRYs translocate into the nucleus and repress their own transcription by interfering with the activity of BMAL1/CLOCK. Finally, degradation of PER/CRY complexes gradually relieves the inhibition, and a new transcriptional cycle can start.