The alpha-2 adrenergic receptor (α-2 AR) agonists have a long history of use in treating different clinical conditions, such as hypertension, psychiatric entities (e.g., attention-deficit hyperactivity disorder), chronic pain, panic disorders, and, lately, for treating opioid withdrawal syndrome. In recent years, α-2 AR medications have been administered as adjuncts for managing inflammatory conditions, depression, chronic pain, sleep and cognitive disorders. This review will provide some clinical applications in neuroscience for this class of drugs. Understanding the pharmacological mechanisms is essential to obtaining neurochemical data that demonstrate that α-2 AR agonists have potential clinical significance in neuroscience.