Circadian rhythms are 24 hour temporal patterns of biochemistry, physiology and behavior that are an integral component of eukaryotic life. The molecular circadian clock is a cell autonomous system composed of three conceptual components: a self-sustainable pacemaker that generates 24 hr rhythmicity; an input pathway which allows the clock to be reset and entrained by temporal cues in the environment; and mechanisms of output which regulate molecular and biochemical pathways and ultimately translate to rhythms in physiology and behavior. The master circadian pacemaker resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. It appears the most critical property of circadian clocks is the ability to anticipate environmental changes which can enable organisms to adapt and organize their physiology and behavior such that it occurs at biologically advantageous times of the day. It is now known that there are oscillators scattered throughout the body in almost all the peripheral tissues The peripheral oscillators of the mammalian system, found within the liver, heart lungs retina and kidney to name but a few are the least well understood concept of the circadian system to date. Since the master clock is situated in the SCN and this is the only clock that can be entrained by light, this suggests a hierarchical model of pacemakers within the mammalian system The ÌÄå¢Ì¢åâåÂÌÜåÏInhibitor of DNA Binding' (ID) proteins are a family of Helix-Loop-Helix (HLH) factors that have been previously implicated in cell cycle, apoptosis and development. They are defined as dominant negative regulators of transcription since they do not contain a basic domain adjacent to the HLH motif, therefore they cannot bind to DNA. Data recently published by our laboratory revealed that Id2-/- mice exhibit a more rapid re-entrainment to a large change in their photoschedule along with greater phase shifts compared to their wild-type counterparts. This data suggests that Id2 is involved in entrainment within the mammalian clock. At the molecular level, ID1, ID2 and ID3 exhibit a marked dose dependent suppression of CLOCK-BMAL1 induced activation of the clock gene mPer1 and CCG Arginine Vasopression (AVP). This suggests a role for the ID proteins as transcriptional repressors within the mammalian clock. Chapter 2 provides evidence for a role for ID2 at the level of the core oscillator demonstrating interaction, specifically direct interaction between ID2 (and ID1 and ID3) with both of the canonical clock proteins CLOCK and BMAL1. A discussion of the input pathway and a molecular model for resetting is also provided. Chapter 3 illustrates that ID2 has a role within the liver tissue as a regulator of clock output. Chapter 4 demonstrates a similar role for ID2 within the heart tissue, suggesting that ID2 is a clock output regulator throughout in multiple tissues/organ systems. In conclusion, the findings of this work outlined within this dissertation indicate a function role within the core oscillator and a physiological role for ID2 within the circadian rhythms of clock gene expression within the mammalian system.