Gastroesophageal reflux disease is a chronic disorder that requires long-term therapy in most patients. The appropriate medical therapy should be individualized to the severity of symptoms, the degree of esophagitis and the presence of other acid-reflux complications. Lifestyle changes should form the basis of any therapeutic approach. In patients with mild to moderate disease, initial therapy with histamine H2-receptor antagonists in conventional dosages is suggested. Prokinetic agents are potentially useful in patients with impaired esophageal or gastric motor function, but their efficacy as single agents does not appear to surpass that of standard doses of H2 blockers. Sucralfate, a cytoprotective agent, is an additional therapeutic option. For patients with more severe disease, omeprazole and lansoprazole provide unequaled healing rates and accelerated symptom relief. In most patients, maintenance therapy is vital. Surgery is indicated in patients whose disease is refractory to medical therapy and in those who develop complications not amenable to medical therapy.