Diseases of the upper gastrointestinal tract, which includes the esophagus, stomach, and duodenum, are common, and they may impact quality of life, morbidity, and mortality. They include congenital disorders such as esophageal websEsophageal webs and diverticuli, infectious disorders such as peptic ulcer disease, motility disorders such as achalasia, and gastric injuries due to chemical ingestion. Underlying disease mechanisms and prognosis for most of these disorders are well described. Diagnostic modalities have evolved substantially in the past decades: examples are the expansion of high-definition endoscopy for Barrett’s esophagus, endoscopic ultrasound for tumor detection, and elaborate functional testing for motility disorders. Similarly, therapeutics have evolved, with the arrival of new acid suppression drugs for gastritis and peptic ulcer disease, endoscopic myotomy for achalasia, and advanced endoscopic therapies for Barrett’s esophagus and gastrointestinal bleeding. Many of the conditions discussed in this section are readily treated and are associated with normal life expectancy or with minimal extra mortality. Others are associated with additional morbidity, and yet others are associated with comorbidities that have a bearing on both.