Sedation is fundamental to the safe and successful performance of gastrointestinal endoscopy in children, although no single sedative or combined sedation regimen has yet to be established as ideal. General anesthesia and moderate sedation remain the two primary options for endoscopy in both children and adults. General anesthesia requires the presence and expertise of an anesthesiologist or certified registered nurse anesthetist and may involve inhalational or intravenous anesthetics. Moderate sedation, aimed at maintaining the child’s ability to breathe spontaneously with intact protective airway reflexes, almost always utilizes intravenous sedatives and may be administered by a physician or nurse, in the absence of an anesthesiologist. In the current era, sedation for pediatric endoscopy, whether administered by endoscopists or anesthesiologists, remains a greater risk to patient safety when compared with other typical risks, such as bleeding, perforation, and infection. Improving efficacy and safety for the sedation of gastrointestinal procedures is, therefore, a topic of great interest among pediatric gastroenterologists.