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Sedation enhances the technical performance of colonoscopy and improves patient tolerance and satisfaction, but engenders costs and complications. Sedation occurs along a continuum, with four stages based on responsiveness to stimulation, airway adequacy, ventilation, and circulation. These include: minimal sedation, moderate sedation, deep sedation, and general anesthesia. During colonoscopy, most endoscopists target moderate sedation. The ideal sedation agent for colonoscopy should possess sedative, analgesic, and amnestic properties and permits rapid onset and fast recovery. Satisfactory unsedated or minimally sedated colonoscopy may be enhanced by pediatric colonoscopes, variable stiffness instruments, three-dimensional magnetic imaging guides, and robotic colonoscopy. A pre-colonoscopy evaluation, designed to assess risk of sedation-related complications, is fundamental to procedure safety. Staffing for colonoscopic sedation may vary based on the agent(s) used, the sedation level targeted, and institutional and jurisdictional guidelines. Sedation has risks, benefits, and alternatives and should be discussed during the pre-procedure informed consent.