The metabolite NAD+ oscillates in a circadian manner. The circadian clock machinery controls the cyclic synthesis of NAD+ through control of the NAD+ salvage pathway (Eckel-Mahan and Sassone-Corsi 2009; Nakahata et al. 2009; Ramsey et al. 2009). The gene encoding the enzyme NAMPT, the rate-limiting step in the NAD+ salvage pathway, contains E-boxes and is controlled by CLOCK–BMAL1. A crucial step in the NAD+ salvage pathway is controlled by SIRT1, which also contributes to the regulation of the Nampt promoter by associating with CLOCK–BMAL1 in the CLOCK chromatin complex. Thus, the feedback transcriptional loop of circadian regulation is intimately linked to an enzymatic feedback loop. Through this regulation, SIRT1 controls the cellular levels of its own coenzyme NAD+. (NAD+, nicotinamide adenine dinucleotide; NAM, nicotinamide; NMN, nicotinamide mononucleotide; ∼, oscillation of CCGs [Nampt] and metabolites [NAD+].) Other connections with critical metabolic pathways are also indicated.