The proton pump inhibitors are a very effective drug group for the control of gastric acid secretion, which makes them of great use in the medical practice setting, while at the same time they represent one of the treatment groups widely used in Western European countries. These factors lead to this drug group being prescribed in all age populations, quite often in polymedicated patients and with pluripathology, and on many occasions during prolonged periods of time. All these determinant factors sometimes make the safety profile of proton pump inhibitors disputable. In this respect all of them have been shown to have little adverse events and are safe in long-term treatment. The risk of drug interactions when prescribed in association with other drugs is low and their repercussion in the medical practice setting is quite exceptional as they require few dosage adjustments in patients with severe concomitant diseases and in elderly patients. Finally, their safety is high in pregnant women and in children, although further studies in this population are required to corroborate this evidence.