Opioids such as morphine are often used early in patients subsequently diagnosed with gastroesophageal reflux disease (GERD). Antacids provide GERD relief by buffering the refluxed gastric contents. Antacids are readily available, relatively safe, and fast acting. Antacids constitute first-line GERD therapy in pregnancy. Proton pump inhibitors (PPIs) are a first-line treatment for non-cardiac chest pain, and for GERD in particular. H2-receptor antagonists such as ranitidine (150 mg PO as needed for GERD pain) have been shown in double-blinded trials to achieve better on-demand pain relief than antacids. Prokinetic drugs such as metoclopramide and cisapride are postulated to relieve GERD by increasing resting lower esophageal sphincter tone and increasing gastric emptying. The novel prokinetic agent itopride has promising preliminary results in an open-label GERD trial, but recommendation for its acute care use must await further data.