Increasing intragastric pH: Effective treatment of acid-related disease requires an increase in intragastric pH. The two principal pharmacological methods of attaining this goal are (1) using histamine (H-2)-receptor antagonists to block H-2-receptors on the parietal cell and (2) using proton-pump inhibitors to stop acid production acid at its source. H-2-receptor antagonists: H-2-receptor antagonists bind loosely and non-covalently to receptors on the parietal cell. They represented a great advance when they first appeared, bringing relief to many patients and improving the standard of care, with fewer operations and hospitalizations and a generally improved quality of life. However, many patients do not respond to these drugs, either because of the nature of the disease or because of resistance to the agent. Proton-pump inhibitors: Proton-pump inhibitors represent an advance in the therapy of acid-related disease because they inhibit all acid production, no matter what the source of the stimulus, by binding covalently to the proton pump. Compared with H-2-receptor antagonists, the effect of proton-pump inhibition is longer-lasting, faster-acting, and more effective, curing 99% of patients resistant to H-2-receptor antagonist therapy. These properties make proton-pump inhibitors the treatment of choice for acid-related diseases.