The medical treatment of gastro-oesophageal reflux disease is accomplished with the appropriate use of anti-secretory therapy, principally H(2)-receptor antagonists and proton pump inhibitors. In fact, there is a direct correlation between the length of time, in terms of the number of hours per day that the intragastric pH is above 4, and the healing of the oesophagitis. Nowadays, H(2)-receptor antagonists are of limited use as primary treatment, being inferior to proton pump inhibitors in both healing and symptom relief. Although the majority of patients can be effectively managed with carefully titrated doses of proton pump inhibitors, a small number will continue to show difficulty in the management of their disease, principally because of inadequate nocturnal acid control. These patients may benefit from a combination of proton pump inhibitors twice daily with an H(2)-receptor antagonist at bedtime. This article reviews the use of H(2)-antagonists, proton pump inhibitors and their combination in the management of the patient with gastro-oesophageal reflux disease.