Epigastric pain can have multiple etiologies including myocardial infarction, pancreatitis, acute aortic syndromes, gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, and hiatal hernia. This document focuses on the scenarios in which epigastric pain is accompanied by symptoms such as heartburn, regurgitation, dysphagia, nausea, vomiting, and hematemesis, which raise suspicion for gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, or hiatal hernia. Although endoscopy may be the test of choice for diagnosing these entities, patients may present with nonspecific or overlapping symptoms, necessitating the use of imaging prior to or instead of endoscopy. The utility of fluoroscopic imaging, CT, MRI, and FDG-PET for these indications are discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.