Proton pump inhibitor (PPI) is the strongest inhibitor to gastric acid secretion. PPI is effective in all gastricacid disorders, such as: peptic ulcer, gastroesofageal reflux disease, non steroid anti inflammatory drugs (NSAIDs)gastropathy, and Zollinger-Ellison syndrome. Several studies comparing one PPI to another. Although somedifferences have been reported, there are small differences with unclear clinical importance.PPI has side effects that may be related to diarrhea due to Clostridium difficile, pneumonia, hip fracture, vitamin B12 deficiency, and IgE mediated allergic reaction. Several studies revealed strong association but havelimitation in design and sampel size. PPI therapy should be according to indication, dose, and appropriate period.