Antisecretory drugs are major tools for management of the Zollinger-Ellison syndrome (ZES). Cimetidine was first used as a successful substitute of total gastrectomy. However with high dosage side effects and an escape from control were observed. As a more potent H2-receptor antagonist ranitidine has obvious advantages and is still largely used. Famotidine is more promising with a longer duration of action and given at lower dosages. Omeprazole could be considered as a treatment of choice with specific action on the proton pump and no side effects. However, with this drug the danger of permanent hypergastrinaemia being associated with fundic carcinoïd induction should be appreciated. Long-acting somatostatin has theoretical advantages in reducing simultaneously acid and gastrin secretion with a potential antitrophic effect. Larger studies are needed to precisely assess the therapeutic potential of the last three drugs.