The epidemic of gastroesophageal reflux disease (GERD) in industrialized nations is currently spreading to less-developed ones, with more than half of the patients having symptomatic or mild erosive GERD. The long-term management of GERD has been dominated by daily maintenance treatment with proton pump inhibitors (PPI) to prevent relapse. It is common, however, for many patients with mild disease and infrequent symptom relapses to use a PPI only when symptoms demand. Patients with symptomatic or mild erosive GERD are therefore ideal for on-demand or intermittent treatment. The efficacy of such a strategy of intermittent treatment, or treatment of symptoms on demand, has recently been evaluated in four randomized controlled studies. These trials demonstrate that such therapeutic strategies reduce symptoms, improve quality of life, and are cost effective. In clinical practice, the author has found these treatment strategies suitable for approximately 60% of newly diagnosed patients with GERD for the long-term management of symptomatic GERD of mild or moderate severity.