Acid-related disorders are common management problems in clinical practice. The key to effective management is successful suppression of gastric acid production. Proton pump inhibitors (PPIs) are the most potent acid suppressants available and are significantly more effective than histamine H(2) receptor antagonists. Although PPIs are highly effective as a class, differences in their pharmacokinetics, such as bioavailability, elimination half-life and metabolism, may translate into differences in clinical outcomes. A new immediate-release omeprazole has been introduced, which allows rapid absorption. This has been shown to produce significantly better nocturnal gastric acid control than delayed-release tablets. The bioavailability of rabeprazole on day 1 is greater than with other PPIs, and this may translate into faster onset of symptom relief for patients with gastro-oesophageal reflux disease. On the other hand, the bioavailability of esomeprazole increases 3-fold at day 5, and it has been shown that on day 5, esomeprazole provided significantly more effective control of gastric acid than other PPIs. The exact clinical significance of these observations remains to be determined. There is genetic polymorphism in PPI metabolism via cytochrome P450 2C19. In Helicobacter pylori eradication, a significantly lower eradication rate was seen in extensive metabolisers with omeprazole and lansoprazole but not with rabeprazole. The oesophagitis healing rate was lower in extensive metabolisers with lansoprazole but not with rabeprazole. The currently available PPIs have short elimination half-lives ranging from 1 to 1.5 hours. Tenatoprazole is a new PPI that has a 5- to 7-fold longer elimination half-life than current PPIs. It could be potentially more useful for the treatment of gastro-esophageal reflux disease and nocturnal acid breakthrough than other PPIs.