In this paper, the current knowledge about the role of histamine in the control of gastric acid secretion is reviewed. In particular, we focus this topic into three sections considering the recent insights on: histamine receptor subtypes involved in gastric acid secretion, the interplay between neuronal-hormonal-paracrine pathways and the cerebral histaminergic control of gastric secretion. From the careful perusal of scientific literature, the fundamental role of histamine as local stimulator of gastric acid secretion via H(2) receptors is fairly confirmed while for the H(3) receptor only a minor modulating role is hypothesized. An undisputed function of ECL cells as controllable source of histamine within the so-called gastrin-ECL cell-parietal cell axis is generally proposed and the intriguing possibility of a remote control of gastric secretion via H(3) receptors is also suggested.