The introduction, in the last two decades, of strongly effective acid suppressant drugs, such as proton pump inhibitors has radically modified the way of treating gastro-oesophageal reflux disease. In clinical trials, these agents have constantly been demonostrated to be more effective than other acid-suppressant agents such as H2-receptor antagonists in relief of symptoms and healing of oesophagitis, the two main goals of gastro-oesophageal reflux disease treatment. They provide a prompt clinical benefit to most patients and can be safely used in long-term gastro-oesophageal reflux disease management for maintenance of clinical and endoscopic remission, because of their negligible adverse-events profile. Therapeutic protocols vary depending on the severity of symptoms and the degree of oesophageal injury. In patients with mild symptoms and with minimal lesions at endoscopy, a "step-down" therapy, in the short-term, is considered the best medical strategy, while in the long-term the therapy "on-demand" appears to be a reasonable approach. Patients with non-erosive disease seem to have a lower response rate to proton pump inhibitor treatment. More severe grades of oesophagitis must be treated with full-dose proton pump inhibitors without withdrawal. Data on the treatment of extra-oesophageal manifestations of gastro-oesophageal reflux disease are few and controversial. Overall, it appears that patients with extra-oesophageal symptoms of gastro-oesophageal reflux disease must be treated with higher doses of pharmacological treatment, principally with proton pump inhibitors, and with longer periods of treatment to achieve complete relief of symptoms, as compared with patients with typical symptoms of gastro-oesophageal reflux disease and erosive oesophagitis