PPI are usually prescribed to avoid drug induced gastropathy. This procedure showed to be effective for NSAIDs, but not for steroids, anticoagulants, antineoplastic agents, antibiotics. PPI intake is related to an increased risk of intestinal and lung infections in the short time, and fracture after one year.PPI are symptomatic drugs for gastroesophageal reflux disease, taken when really necessary (with scheme “as needed “) at the lowest possible dose. In this case, the main therapy discontinuation risk is the intensification of symptoms, which may eventually require a cyclic intake. Some studies have suggested a possible utility of long- term therapy with PPIs in preventing neoplastic degeneration of Barrett’s esophagus. These patients require special cautions.