Neuropeptide CART is highly expressed in the CNS and is known for its remarkable potential to reconfigure neural circuits for behavioral demands. The functional significance of CART and how it operates the neural circuits to drive behavior are poorly understood. I explored the neurochemicals and signaling systems employed by CART neurons, determined the mechanism through which CART-containing systems drive behavior, and identified the conserved CARTergic neuroanatomical substrates. Three subtypes of CART neurons were observed in the hypothalamus. Secretagogin, highly expressed in the entopeduncular CART neurons, mediates the effect of insulin. CART drives the nigrostriatal DA pathway and motor coordination via the activation of TRPV2. Although CART is highly expressed in each node of the aggression circuit in male as well as female rats, a subset of CART neurons in the hypothalamic attack area drives maternal but not inter-male aggression. CART peptides and the neuroanatomy of CART-containing elements in the brain showed conserved features. Unlike mammals, CART neurons were found in two distinct subdivisions in the arcuate nucleus of a reptile. This study identifies a novel role of CART in driving aggressive actions. CART may influence neural circuits and behavior directly or via modulation of the DA-/glutamatergic pathways, and may serve as a preferred central regulator in the CNS across vertebrates.