The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin.