Proton-pump inhibitors (PPIs) are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a newgeneration PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy.Key words: Proton-pump inhibitor. PPI. Omeprazole. Pantoprazole. Lansoprazole. Rabeprazole. Esomeprazole. INTRODUCTIONProton-pump inhibitors (PPIs) represent a family of drugs widely used in our country. The advent in the nineties of PPIs was a great revolution in the treatment of ulcer disease and gastroesophageal reflux. The main problems of PPIs at present time are its overuse and the errors in the therapeutic indication. This fact leads to a considerable health economic cost and the risk of long-term side effects. In this review the main problems of PPIs prescription, their indications, the differences between PPIs and tips on their use are discussed. Brief historical memory: since alkaline diets until PPIsThe treatment of ulcer disease and gastroesophageal reflux disease (GERD) in the early twentieth century was the prescription of alkaline foods like milk, eggs and puree (1). Later, there were products as sodium bicarbonate that improved symptoms but did not prevent complications. Surgical treatment consisted of different types of gastric surgeries for peptic ulcer disease and Nissen fundoplication for GERD (2).In the mid twentieth century the use of muscarinic antagonists was introduced, atropine being its main active ingredient. Acids secretion was partially inhibited by blocking the muscarinic receptor of the parietal cell. However, these drugs had little effectiveness and numerous adverse effects due to the amount of muscarinic receptors distributed throughout the body. E-type prostaglandin was discovered later, but, again, the limitations of these substances were their short half life and side effects. An important progress in gastric antisecretory therapy was the appearance of H 2 receptors antagonists (H 2 blockers) (3). The most used were ranitidine and famotidine. These drugs established a substantial change by blocking the action of histamine receptor in gastric parietal ...