To review recent literature on the safety and efficacy of dexmedetomidine. Articles were identified through searches of MEDLINE (1966-January 2007). Key words included dexmedetomidine, medetomidine, alpha(2)-agonist, and sedation. References from selected articles were reviewed for additional references. Experimental and observational studies that focused on the safety and efficacy of dexmedetomidine in humans were selected. Dexmedetomidine is an alpha(2)-agonist for short-term sedation in critically ill patients. In postoperative patients, dexmedetomidine produced similar levels of sedation and times to extubation, with less opioid requirements compared with propofol. Dexmedetomidine has also been studied for sedation in critically ill medical and pediatric patients, as adjunct to anesthesia, and for procedural sedation. Hypotension, hypertension, and bradycardia are common adverse effects. Although dexmedetomidine is labeled only for sedation less than 24 hours, it has been administered for longer than 24 hours without apparent development of rebound hypertension and tachycardia. Dexmedetomidine is a safe and effective agent for sedation in critically ill patients. Further, well designed studies are needed to define its role as a sedative for critically ill medical, neurosurgical, and pediatric patients, as an adjunct to anesthesia, and as a sedative during procedures.