Figuring out how metabolism is modulated by environmental and nutritional cues is a task of great conceptual and pharmacological interest. In this respect, an element that occupies a critical position is time. A remarkable array of fundamental physiological functions are circadian in nature, that is, they follow an approximately 24-h cycle. Remarkably, this is the case in almost all organisms, from prokaryotes and plants to humans (Cermakian and Sassone-Corsi 2000; Reppert and Weaver 2001; Bell-Pedersen et al. 2005). The circadian clocks are intrinsic time-tracking systems with which organisms can anticipate environmental changes and adapt themselves to the appropriate time of day (Reppert and Weaver 2001; Young and Kay 2001). In mammals, circadian rhythms are generated in pacemaker neurons within the suprachiasmatic nuclei (SCN) of the hypothalamus. Conceptually, the pacemaker receives input signals, such as light from the retina, and processes them into outputs. These can be the expression of clock-controlled genes (CCGs) or metabolites, which—as we propose here—may feed back on the pacemaker (Fig. 1). Disruption of these rhythms can have a profound influence on human health and has been linked to metabolic disorders, insomnia, depression, coronary heart diseases, various neurodegenerative disorders, and cancer (Sahar and Sassone-Corsi 2009; Bechtold et al. 2010). Recent years have witnessed a spectacular increase in research on biological rhythms, specifically the molecular mechanisms of the circadian clock. These studies have established some intriguing links between the clock and cellular metabolism, endocrine control, and transcriptional and epigenetic regulation.