The production of acid by the stomach is a tightly controlled physiological process that involves neural and hormonal mechanisms and the input of several epithelial cell types. The past several years have seen significant advances in our understanding of the molecular ontogenesis of the stomach and the factors controlling stomach innervation, as well as the differentiation of gastric epithelial cell lineages and their respective hormones/factors that influence acid production. The programmed development of each of these elements is exquisitely regulated and allows human neonates to produce gastric acid; it also helps us define expectations of acid production in preterm infants at all gestational ages.