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The role of dexmedetomidine for the management of pain, agitation, and delirium in adult patients in the intensive care unit (ICU) is reviewed and updated.Searches of MEDLINE (July 2006–March 2012) and an extensive manual review of journals were performed. Relevant literature with a focus on data published since our last review in 2007 was evaluated for topic relevance and clinical applicability. Optimal management of pain, agitation, and delirium in ICUs requires a systematic and multimodal approach aimed at providing comfort while maximizing outcomes. Dexmedetomidine is among multiple agents, including opioids, propofol, benzodiazepines, and antipsychotics, used to facilitate and increase patients' tolerability of mechanical ventilation. This article reviews the newest evidence available for dexmedetomidine use for sedation and analgesia in medical–surgical ICUs. Adverse effects associated with dexmedetomidine were similar among the studies examined herein. The most common adverse effects with dexmedetomidine were bradycardia and hypotension, in some cases severe enough to warrant the use of vasoactive support. Due to the adverse events associated with rapid dosage adjustment and bolus therapy, dexmedetomidine may not be the best agent for treating acute agitation.In medical–surgical ICUs, dexmedetomidine may be a viable non-benzodiazepine option for patients with a need for light sedation. In cardiac surgery patients, dexmedetomidine appears to offer no advantage over propofol as the initial sedative. The role of dexmedetomidine in unique patient populations such as neurosurgical, trauma, and obstetrics is yet to be established.