The proton pump inhibitors (PPIs) are a relatively new class of agents used for the treatment of acid-related disorders, including peptic ulcer diseases, reflux oesophagitis and Zollinger-Ellison syndrome, and in enhancing antibiotic therapy in the eradication of Helicobacter pylori in patients with peptic ulcer disease. The PPIs are the most potent gastric acid-suppressing agents currently in clinical use. According to the recent basic study, PPIs may act not only as potent acid suppressants, but also as anti-inflammatory or pro-regenerative agents. On the other hand, in the clinical field, general practitioners still tend to prescribe PPIs for unlicensed indications, such as non-ulcer dyspepsia and nonspecific abdominal pain. This article reviews the novel pharmacological action other than acid secretion and the diverse clinical usage of PPIs, in order to seek possible extensions of the use of this unique agent.