Abstract The α-2 adrenergic receptor agonists have been used for decades to treat common medical conditions such as hypertension; attention-deficit/hyperactivity disorder; various pain and panic disorders; symptoms of opioid, benzodiazepine, and alcohol withdrawal; and cigarette craving.1 However, in more recent years, these drugs have been used as adjuncts for sedation and to reduce anesthetic requirements. This review will provide an historical perspective of this drug class, an understanding of pharmacological mechanisms, and an insight into current applications in clinical anesthesiology.