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Current choices for sustained sedation in the critically ill include the benzodiazepines, the opiates, and propofol. Each of these groups of medications has their particular benefits: benzodiazepines provide the greatest amnesia, opiates are the only agents to provide analgesia, and propofol is the most easily titratable and the least likely to excessively accrue. The literature seems to favor propofol over the benzodiazepines as the most cost-effective solution to sustained sedation. A newly approved agent, dexmedetomidine, holds promise as a continuous infusion that can provide both anxiolysis and analgesia, but without the ventilatory depression seen in the other classes of sedatives. Further research is needed to determine the role of dexmedetomidine in the ICU. The emerging standard of care for sustained sedation is the use of standardized protocols, formulated with the help of clinical practice guidelines, and titrated with the guidance of sedation monitoring.