Background and Aims: The alpha-2-adrenergic agonist drugs are now widely used in anesthesiology for multiple purposes and are not limited only to intraoperative and postoperative analgesia. Clonidine, an imidazoline derivative belongs to this class and has selectivity ratio of 200:1 for alpha-2: alpha-1 receptors. Contents: Apart from its antihypertensive and anti-adrenergic effects, recent studies have established clonidine as a wonder drug to be an effective analgesic, sedative and has an opioid sparing effect with decreased anesthetic requirements intraoperatively. Therefore, a detailed analysis and discussion for possible new role of clonidine in anesthetic armamentarium seems to be need of the hour. This review highlights pharmacological aspects, mechanisms of action, opioid sparing effect, potential indications and adverse effects. Conclusion: Although Clonidine reduces post-operative pain intensity and nausea apart from some other uses like alcohol withdrawal, acute hypertension, smoking cessation, cancer pain management and adjuvant to local anesthetics. However, one should be vigilant while using it for high risk of perioperative low blood pressure and bradycardia.