A variety of abnormalities contribute to the development of gastroesophageal reflux disease (GERD) including transient lower esophageal sphincter relaxation, low esophageal sphincter pressure, presence of a hiatal hernia, diminished esophageal clearance of refluxed gastric contents, and alterations in esophageal mucosal resistance. Helicobacter pylori infection clearly plays a role in the pathogenesis of peptic ulcer disease and mucosa associated lymphoma of the stomach and is a definite risk factor for distal gastric cancer. The role of H. pylori infection in GERD remains controversial and incompletely understood. Although H. pylori infection does not cause reflux disease, circumstantial evidence suggests that it may protect against the development of GERD and its complications in some patients. The most likely mechanism whereby H. pylori infection protects against GERD is by decreasing the potency of the gastric refluxate in patients with corpus predominant gastritis. A variety of implications of H. pylori infection on GERD treatment have also arisen in recent years. These focus on the risk of gastric atrophy while on proton pump inhibitor therapy and the efficacy of proton pump inhibitors before and after eradication of H. pylori. This article puts into perspective our current understanding of the complex, incompletely understood relationship between H. pylori infection and GERD.