Prior to any rational therapy of gastro-esophageal reflux disease, an objective diagnosis of the presence and the cause of the disease are necessary. Gastro-esophageal reflux disease, i.e., increased esophageal exposure to gastric juice, can be due to a mechanically defective lower esophageal sphincter, inefficient esophageal clearance of refluxed gastric contents, and abnormalities of the gastric reservoir that augment physiologic reflux. Antireflux surgery is designed to correct a mechanically defective sphincter, i.e., a sphincter with a mean pressure below 6 mm Hg, a mean length exposed to the positive pressure environment of the abdomen of less than 1 cm, or a mean overall length of less than 2 cm. In our experience, this is found in approximately 50% to 60% of patients with gastro-esophageal reflux disease. Antireflux surgery is not indicated in patients with increased esophageal exposure to gastric juice secondary to ineffective clearance or gastric abnormalities. Consequently, the indications to proceed with an antireflux procedure are persistent or recurrent symptoms and/or complications of gastro-esophageal reflux disease after 8 to 12 weeks of intensive acid suppression therapy, the objective documentation of increased esophageal exposure to gastric juice with 24 hour esophageal pH monitoring, and the presence of a mechanically defective lower esophageal sphincter on manometry. In patients selected according to these criteria, Nissen fundoplication provides effective relief of reflux symptoms in 91% of patients with more than 10 year follow-up.