Alpha 2 adrenergic agonists will soon be used in the anesthetic management for their sedative/hypnotic, anesthetic-sparing, analgesic and sympatholytic properties. But the clinically available alpha 2 agonists have unwanted side-effects such as acute hypertension and bradycardia following a bolus injection because these agonists do not discriminate between the 3 alpha 2 adrenoceptor subtypes. Molecular biological methods can identify mediating receptor subtype for each response. Knockout mice study reveals that the alpha 2 B adrenoceptor subtype mediates the hypertensive response to alpha 2 agonists. Knockdown study using the antisense technology demonstrates that the alpha 2 A adrenoceptor subtype mediates the hypnotic and analgesic effects of alpha 2 agonists. The next generation of alpha 2 agonists should be alpha 2 A selective to maximize anesthetic and analgesic effects while minimizing hypertensive response.