Proton pump inhibitors (PPI) are very effective in inhibiting acid secretion and are extensively used in many acid related diseases. They are also often used in patients with cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment. Contradicting reports support their use in cirrhosis and evidence of their efficacy in this condition is poor. Moreover there are convincing papers suggesting that acid secretion is reduced in patients with liver cirrhosis. With regard to Helicobacter pylori (H pylori) infection, its prevalence in patients with cirrhosis is largely variable among different studies, and it seems that H pylori eradication does not prevent gastro-duodenal ulcer formation and bleeding. With regard to the prevention and treatment of oesophageal complications after banding or sclerotherapy of oesophageal varices, there is little evidence for a protective role of PPI. Moreover, due to liver metabolism of PPI, the dose of most available PPIs should be reduced in cirrhotics. In conclusion, the use of this class of drugs seems more habit related than evidence-based eventually leading to an increase in health costs.