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We provide an overview of the immunological effects of commonly used anesthetic drugs and highlight their potential impact on long-term outcome after surgery.Clinical trials provide preliminary evidence that the perioperative process can influence long-term patient outcome. Immunology may begin to elucidate the biology of this safety concern and open new therapeutic opportunities. In this context, awareness of the immunological properties of drugs administered in the perioperative period may assist in their deliberate use to modulate this risk. Statins, β-blockers, and clonidine can potentially improve long-term cardiac risk. Volatile anesthetics appear to suppress effector functions of both the innate and adaptive immunity, assist tumor growth in animal models, and facilitate aggregation of certain neurodegenerative disease proteins. Local anesthetics block neurons, but are also potent antiinflammatory drugs. Morphine has recognized immunosuppressive functions, which the newer, synthetic opioids don't seem to share. The cholinergic nervous system has antiinflammatory control functions that are largely unexploited.Long-term outcome after surgery is a new safety concern in perioperative care. We are faced with enormous challenges in healthcare and research. As providers, tailoring an anesthetic plan to patients' needs will become increasingly critical, and immunology should help in this pursuit.