Proton pump inhibitors irreversibly inhibit the enzyme hydrogen-potassium adenosine triphosphatase (H(+)-K(+)-ATPase), which suppresses acid production in the parietal cell of the stomach. Omeprazole, the prototype proton pump inhibitor, has proved to be very effective. However, newer agents are being designed to provide even more potent acid suppression and longer-acting proton pump inhibition, with the goal of further controlling gastric hypersecretion. Lansoprazole is the second proton pump inhibitor available on the market. Pantoprazole is not yet available for general use in the United States. However, each of these drugs is slightly different from omeprazole, thus offering some possible clinical advantages. Compared with omeprazole, lansoprazole has a longer duration of action and improved activity against Helicobacter pylori, while pantoprazole has less interaction with the cytochrome P-450 system and more predictable bioavailability. All three agents have similarly high healing rates for acid peptic diseases and appear to be superior to histamine2-receptor antagonists.