Proton pump inhibitors (PPIs) represent drugs of first choice for treating acidrelated disorders such as: peptic ulcer (PU), gastrooesophageal reflux disease (GERD), Zolliger-Ellison syndrome and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal leasions. The success of PPIs is due both to their clinical efficacy and excellent safety profile. Five PPIs are now available: omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. All of them suppress gastric acid secretion by blocking the H+/K+ adenosine triphosphatase. Whereas pharmacodynamic profile of PPIs is almost the same, some physicochemical and pharmacokinetics differences exist among these five drugs that can influence their clinical action because of close relationships between pharmacokinetics, pharmacodynamics and therapeutic outcome. The aim of this paper was to review the pharmacokinetics, pharmacodynamics, clinical use and main adverse events of PPIs with a focus on similarities and differences among them that might influence their clinical utility.