Proton pump inhibitors have dramatically influenced the management of acid-peptic disorders in recent years. They all have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4. There is some variation in their potential for drug interactions due to differences in enzyme inhibition. Relatively few serious adverse effects have been reported for the proton pump inhibitors. Comparative studies of acid suppression suggest that lansoprazole and pantoprazole have a potency similar to that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset of maximal acid suppression than the other proton pump inhibitors. Comparative studies using proton pump inhibitors for the treatment of reflux oesophagitis, duodenal ulcer healing and Helicobacter pylori eradication show little overall difference in outcome between the proton pump inhibitors when used in their standard doses. Lansoprazole and rabeprazole provide earlier and better symptom relief than the other proton pump inhibitors in some studies of peptic ulcer treatment. The few studies of gastric ulcer treatment suggest that there is an advantage in using the proton pump inhibitors that have a higher standard daily dose.