Symptomatic gastro-oesophageal reflux disease is a common disorder characterized by pathological exposure of the distal oesophagus to acid. The management requires the control of symptoms, prevention of relapse and complications. Proton pump inhibitors are without doubt the most effective agents in the management of gastro-oesophageal reflux disease. In Helicobacter pylori-negative individuals the efficacy of ranitidine, but more pronounced of omeprazole, on the nocturnal intragastric acidity, is less than in Helicobacter pylori-positive patients. Curing the Helicobacter pylori infection in gastro-oesophageal reflux disease patients might, therefore, have the disadvantage of losing efficacy of antisecretory therapy. Conversely, several studies have shown that long-term use of proton pump inhibitors is associated with progression and worsening of body gastritis exclusively in Helicobacter pylori-positives. This observation makes Helicobacter pylori eradication indicated before starting long-term treatment with proton pump inhibitors for gastro-oesophageal reflux disease and other acid-related diseases. The data reported, so far, however, are not conclusive. The Federal Drugs Administration Advisory Committee concluded on available data, that there is no evidence that longterm proton pump inhibitors treatment leads to gastric atrophy, intestinal metaplasia or gastric cancer. Eradication of Helicobacter pylori infection might lead to reduction in the efficacy of antisecretory agents, but might prevent worsening of the gastric corpus gastritis. More data are needed to really answer these clinically relevant questions.