Although glucagon is the most commonly used pharmacologic agent for gastrointestinal studies, its exact effects on upper gastrointestinal examinations have not been properly elucidated. A large study by our group did redemonstrate glucagon's significant effect on gastrointestinal motility. However, gastric distention and coating are not improved by glucagon, nor does it have a predictable effect on gastric emptying. Duodenal visualization does appear to be enhanced by the drug. Patient age, weight, and sex are not significant factors in glucagon's response, although they are variables that have an effect on UGI examinations. This article will review physiologic considerations in upper gastrointestinal examinations, with emphasis on glucagon's pharmacodynamics.