At this time, the unique attributes of alpha 2-agonists in anesthesia lie in their ability to blunt the adrenergic response to the stresses of major surgery, in patients in whom this response is especially undesirable, without incurring the penalty of respiratory depression that attends the use of opioids. It has become more and more apparent that sympathetic/adrenergic activation often has adverse consequences for patient morbidity and mortality, and modification of such activation by drugs may be a valuable option for the anesthesiologist. However, at present, the evidence supporting this statement is "soft," such as improved hemodynamic and metabolic stability. What must be done is to generate solid support in the form of well-designed outcome studies. The potential value of alpha 2-agonists is greatest in major surgery in brittle patients involving the risk of significant adverse outcome. There are plenty of adequate anesthesia regimens to cover lesser surgical interventions. In these cases, it is not the choice of a specific anesthetic agent or technique, but rather the competence and diligence of the anesthesiologist that is most important for outcome. In contrast, in major cardiovascular surgery in high-risk patients, the optimal anesthetic approach attains more importance, and is still undecided. The final consensus as to whether or not this optimal approach will include the use of alpha 2-adrenergic agonists will depend on the results of more extensive clinical investigations.