Dexmedetomidine is a selective α2-adrenoceptor agonist that offers unique sedation because patients are readily awakened while administration continues and the drug does not suppress the respiratory center. Limitations of use include higher acquisition cost, inability to produce deep sedation, and bradycardia and hypotension. Using a case-based approach, the purpose of this review was to qualitatively assess the role of dexmedetomidine in the care of the critically ill and in the management of alcohol withdrawal, and to formulate recommendations regarding its clinical application. Sixty-six studies were identified that investigated dexmedetomidine for the provision of sedation. These studies were heterogeneous in design and patient populations; most investigated patients did not require heavy sedation, and few used propofol as the comparator. In general, though, the aggregate results of all studies demonstrate that dexmedetomidine provides comfort, possibly shortens the duration of mechanical ventilation to facilitate extubation, reduces the occurrence of acute brain dysfunction, and facilitates communication, but the drug is associated with hemodynamic instability and requires the supplemental use of traditional sedative and analgesic agents. These outcomes need to be substantiated in additional studies that include assessments of cost-effectiveness. Dexmedetomidine should be considered when patients require mild to moderate levels of sedation of short to intermediate time frames, and they qualify for daily awakenings with traditional sedative therapies. The data for dexmedetomidine in relation to alcohol withdrawal are limited to 12 retrospective reports representing a total of 127 patients. Its role for this indication requires further study, but it may be considered as adjunctive therapy when clinicians are concerned about respiratory suppression associated with escalating doses of γ-aminobutyric acid agonists. Regardless of the indication for dexmedetomidine, the practitioner must closely monitor patient comfort and the occurrence of hemodynamic deviations with the realization that as-needed administration of traditional sedatives and analgesics will be required and some degree of bradycardia and hypotension expected but intervention rarely required.