Gastro-oesophageal reflux disease (GERD) is one of the most common conditions presenting to the primary care physician. Despite progress in understanding and treatment of the disease, strategies for capitalizing on these advances are less well developed. In many practices, H2-receptor antagonists still remain the most widely prescribed treatment for GERD, despite the availability of the more effective acid-suppressant proton pump inhibitors. This review examines the relative efficacies of acid-suppressant drugs in minimizing oesophageal acid exposure and outlines the evidence for the superiority of proton pump inhibitors over standard-dose H(2)-antagonists in symptom relief, erosion healing and prevention of relapse in GERD. Current prescribing patterns and considerations for the general practitioner are also examined. The availability and impact of over-the-counter H(2)-antagonists on the treatment of GERD and their relative cost-effectiveness vs. proton pump inhibitors are also addressed. A hierarchy of drug efficacy (full-dose proton pump inhibitor > half-dose proton pump inhibitor > high-dose H(2)-antagonist > standard-dose H(2)-antagonist or prokinetic) applies in principle to all GERD patients, (with or without oesophagitis). The most effective initial therapy for GERD is also likely to be the most cost-effective one, if treatment failure leads to higher utilization of medical resources. The application of these recommendations to the management of non-endoscoped GERD, endoscopy-negative GERD and low-grade oesophagitis as well as higher grade oesophagitis is also reviewed.