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"The knife is searching for disease, the pulleys are dragging back dislocated limbs, nature herself is working out the primal curse which doomed the tenderest of her creatures to the sharpest of her trials, but the fierce extremity of suffering has been steeped in the waters of forgetfulness, and the deepest furrow in the knotted brow of agony has been smoothed forever."    Dr. Oliver Wendell Holmes, Sr., uttered those words almost 200 years ago, in November of 1846, commenting in a lecture to students at Massachusetts Medical College on the first public demonstration of ether just a month before. The historical event has since become known as "Ether Day." Indeed, when Dr. William Morton, a dentist, successfully anesthetized Mr. Gilbert Abbot with ether for the resection of a tuberculous submandibular lesion in the amphitheater of Massachusetts General Hospital, many shared this belief. Corresponding with Dr. Morton shortly thereafter, Dr. Holmes is believed to have coined the term "anesthesia," stating: " Everybody wants to have a hand in a great discovery. All I will do is to give a hint or two as to names—or the name—to be applied to the state produced and the agent. The state should, I think, be called "Anaesthesia." This signifies insensibility—more particularly...to objects of touch."   The medical community at large assumed then that humanity's unavoidable suffering through surgical intervention—the "primal curse" of humankind—was relegated to the dustbin of medical history. And yet, in the third decade of the 21st century, intraoperative awareness continues to threaten patients with horror and agony on the operating table, even as expectations for painless surgery have become commonplace and as practitioners of anesthesia continue to minimize both its frequency and relevance.  This review will address incidence, risk factors, monitoring of anesthetic depth, strategies for prevention, and perioperative, team-based management of unintended intraoperative awareness. The topic will conclude with a brief review of the long-term effects of accidental awareness during general anesthesia (AAGA) on both patients and practitioners.  Intraoperative awareness is characterized by the coincidence of both intraoperative consciousness and explicit, episodic postoperative recall of events during a planned anesthetic. Patient experiences may range from isolated auditory recall to the catastrophic experience of painful surgical stimulation combined with the sensation of suffocation and paralysis in the setting of neuromuscular blockade (NMB). While the broader phenomenon of intraoperative awareness may occur in any setting where a patient expects a depressed level of consciousness, including in the context of regional anesthesia, procedural or intravenous (IV) sedation, most attention—both from patients and from practitioners--is focused on AAGA. Estimates of the incidence of AAGA range from 1:1000 to 1:20,000, with a wide range of variation dependent upon variables in anesthetic technique, patient population, and surgical context/procedure. Notably, published rates of incidence are highly dependent on the investigational approach, with rates derived from directed postoperative questioning far exceeding those in studies of self-reported awareness., (Copyright © 2022, StatPearls Publishing LLC.)