Relationship between Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD) is controversial. We aimed to review the possible relationship between H. pylori infection and GERD. Epidemiological data indicate an inverse relationship between frequency of H. pylori infection and prevalence of GERD and its complications like Barrett's esophagus and esophageal adenocarcinoma. H. pylori eradication in patients with peptic ulcer disease may be associated with increased risk of development of GERD compared with untreated patients. Infection with cagA bearing strains of H. pylori was associated with less severe GERD including endoscopic esophagitis, possibly due to pangastritis leading to hypochlorhydria. Recent studies on inflammatory markers (IL-1beta and IL-1RN) suggest pro-inflammatory genotypes to be protective against development of severe GERD, especially in patients with H. pylori infection. Identification of candidate genes playing an important role in gastric acid secretion and visceral hypersensitivity to the esophageal epithelium might help in early detection of individuals susceptible to develop GERD. Interplay between H. pylori and host factors play an important role in the pathogenesis of GERD.