This chapter describes earlier observations that lead to the view that there is a precise multiple neurochemical coding of the subpopulations of enteric neurons, which form the intricate neuronal circuits that control intestinal functions. In the mammalian enteric nervous system, there are as many neurons as in the spinal cord, and there are numerous different enteric neurons characterized by the substances they contain, their shapes, and their projections. Most gastrointestinal functions—that is, motility with its vast repertoire of behavior, blood flow, and secretion and absorption of water and electrolytes—are known to be controlled or influenced by autonomic nerves. The discovery of coexistence of chemical messengers in neurons prompted the systematic immunohistochemical investigation of the patterns of coexistence of messengers in enteric neurons. The chapter discusses the methods for the simultaneous localization of two antigens and the problems encountered and demonstrates some of the applications of studies of coexistence of multiple messengers. This principle of organization of the enteric nervous system provides an extremely valuable framework in working out its circuitry and assists in identifying the possible roles of the multiple chemical messengers in individual neurons. The chapter proposes a reevaluation of terminology and notation to encompass the realization that every neuron has multiple chemical messengers and that each neuron may transmit multiple messages.