Acid inhibition is safe and useful in several clinical settings. Proton pump inhibitors are more effective than H2-receptor antagonists in virtually all cases. Proton pump inhibitors should be used in: the eradication of Helicobacter pylori; the treatment of non-H. pylori-related peptic ulcer healing; for the prevention and treatment of non-steroidal anti-inflammatory drug-induced upper digestive lesions; for bleeding peptic lesions; and, especially, in the short-term and long-term control of gastro-oesophageal reflux disease. The timing, the dosing and the specific drugs should be adapted to the particular patient, clinical situation and local factors. For instance, in a patient with active bleeding from a duodenal ulcer, intravenous constant infusion should be the preferred treatment. When seeking oral 'potent' acid inhibition (refractory gastro-oesophageal reflux disease, and perhaps Barrett's oesophagus), available data suggest that the pharmacological and clinical profiles of esomeprazole are slightly better.