CART peptides are important neuropeptides that are involved in a variety of physiologic processes. The regulation of the CART gene is critical since peptides are regulated and secreted in response to specific stimuli. CART mRNA must also be controlled in order to respond to specific stimuli such as psychostimulant drugs and leptin. The regulation of the CART gene is central to maintaining homeostasis of peptide production. The 5′ upstream region of the CART gene contains powerful regulatory elements that must be involved in transcriptional regulation via different signaling pathways. This review touches on several aspects related to CART gene regulation such as: (i) CART genomic structure, (ii) stimuli that alter CART mRNA levels, (iii) promoter characterization, (iv) role of the cAMP/PKA/CREB signal transduction pathway, and (v) role of the CART 5′ and 3′ ends in CART mRNA regulation. The goal of this review is to present current data so as to encourage further work in the field of CART gene regulation.