The proton pump inhibitors (PPIs) are the most successful class of drugs that have been introduced for the treatment of gastro-oesophageal reflux disease (GORD) because of their profound and consistent effect on gastric acid secretion. The PPIs have demonstrated an excellent adverse effect profile after approximately 18 years of clinical use. Healing rates in erosive oesophagitis surpass 90%. Complete symptom resolution is achievable in close to 80% of patients with Barrett's oesophagus. Complications of these conditions, such as oesophageal stricture, ulceration and others, are becoming less frequent because of PPI treatment. In non-erosive reflux disease, PPIs provide 50-65% symptom response rate, which is the highest amongst all currently available anti-reflux interventions. PPIs have also helped to improve success rates in treating patients with atypical/extra-oesophageal manifestations of GORD. The use of PPI treatment as a diagnostic tool for GORD is well accepted. However, PPIs have changed the face of GORD in the new millennium as the focus in gastroenterology practice has shifted to primarily treating patients who fail PPI therapy.