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Progress in medical technology, diagnostic procedures and imaging techniques results in a growing demand for well tolerated sedation regimens, devoid of respiratory and haemodynamic complications. Moreover, rapid turnover time dictates the need for rapid onset of effect and rapid recovery. Recent literature regarding the use of dexmedetomidine, ketamine and remifentanil for sedation outside the operating room is reviewed. As procedural sedation is often performed by nonanaesthesiologists, articles from journals other than anaesthesiology journals are also included.Dexmedetomidine seems an attractive choice for sedation, because of the lack of respiratory depression. It has been studied as a sole sedation agent or in combination with benzodiazepines or opioids. As premedication, it can be administered intranasally. Disadvantages are a rather slow onset and recovery. Bradycardia and hypotension are common. Ketamine got renewed attention mainly by nonanaesthesiologists performing procedural sedation. Psychogenic adverse effects and slow recovery limit its use. Psychiatrists are interested in its antidepressive effect. Ketamine has a potential role in lowering the risk of chronification of pain, modified by analgesic and anti-inflammatory effects. Remifentanil as an ultra-short-acting agent is less well studied outside the operating room. Its unique pharmacology permits its use in patient-controlled analgesia and sedation, in target-controlled infusion or in a combined technique.Recent literature is reviewed regarding dexmedetomidine, ketamine and remifentanil for its use outside the operating room. Sedationists have to keep in mind the pharmacokinetics and pharmacodynamics of the currently used agents in adults and children.