Different anesthetic techniques and drugs can be used for esophagogastroduedonal endoscopy. However, the scientists are still searching for appropriate drugs and protocols for sedation during esophagogastroduedonal endoscopy. The aim of this review is to discuss the topics related with sedation and esophagogastroduedonal endoscopy in the light of literature. Today standard procedure for diagnostic esophagogastroduedonal endoscopy usually consists of topical pharyngeal anesthesia, minimal sedation or anxiolysis, which may be complemented with analgesia when needed. When a prolonged, complex, or particularly troublesome or painful examination is foreseen, deeper sedation with multiple drugs and in closed observation of a staff may be required.