BACKGROUND: The purpose of this study was to review the current management of gastro-oesophageal reflux disease (GORD), including treatment costs, safety profile and effectiveness. METHODS: A literature review was performed of randomized-controlled trials, systematic reviews, Cochrane reports and National/Societal guidelines of the medical, endoscopic and surgical management of GORD. Proton pump inhibitor (PPI) prescribing patterns and expenditure were reviewed in different countries, including Australia, Canada, New Zealand, UK and USA. RESULTS: Proton pump inhibitors (PPIs) are primarily indicated for control of GORD, Helicobacter pylori eradication (combined with antibiotics), preventing NSAID-induced gastrointestinal bleeding and treating peptic ulcer disease. There is widespread overprescribing of PPIs in Western and Eastern nations in terms of indication and duration, with substantial expense for national health providers. Despite a favourable short-term safety profile, there are observational associations of adverse effects with long-term PPIs. These include nutrient malabsorption, enteric infections and cardiovascular events. The prevalence of PPI use makes their long-term safety profile clinically relevant. Cost-benefit, symptom control and quality-of-life outcomes favour laparoscopic fundoplication rather than chronic PPI treatment. Laparoscopic fundoplication in long-term management of PPI-responsive GORD is supported by SAGES, NICE and ACG, and PPI-refractory GORD by AGA and SAGES guidelines. The importance of establishing a definitive diagnosis prior to invasive management is emphasized, especially in PPI-refractory heartburn. CONCLUSIONS: We examined evidence-based guidelines for PPI prescribing and deprescribing in primary care and hospital settings and the need for PPI stewardship and education of health professionals. This narrative review presents the advantages and disadvantages of surgical, endoscopic and medical management of GORD, which may assist in shared decision making and treatment choice in individual patients.This paper was presented (GS020) at the 88th RACS Annual Scientific Conference, 6-10 May, 2019.