Common questions that arise regarding treatment of gastroesophageal reflux disease (GERD) include which medications are most effective, when surgery may be indicated, which patients should be screened for Barrett esophagus and Helicobacter pylori infection, and which adverse effects occur with these medications. Proton pump inhibitors (PPIs) are the most effective medical therapy, and all PPIs provide similar relief of GERD symptoms. There is insufficient evidence to recommend testing for H. pylori in patients with GERD. In the absence of alarm symptoms, endoscopy is not necessary to make an initial diagnosis of GERD. Patients with alarm symptoms require endoscopy. Screening for Barrett esophagus is not routinely recommended, but may be considered in white men 50 years or older who have had GERD symptoms for at least five years. Symptom remission rates in patients with chronic GERD are similar in those who undergo surgery vs. medical management. PPI therapy has been associated with an increased risk of hip fracture, hypomagnesemia, community-acquired pneumonia, vitamin B12 deficiency, and Clostridium difficile infection.