We cast a novel perspective on two distinct populations: patients who become accidentally intraoperatively aware after receiving general anesthesia and severely brain-injured patients who are diagnosed as being in a vegetative state. In both cases, patients are behaviorally non-responsive -and on this basis presumed to lack consciousness- yet, retain covert awareness. In both contexts, detecting consciousness is highly challenging, yet highly important for ensuring adequate patient care. Although great strides have been made in the development of depth-of-anesthesia monitors, these monitors have significant limitations. On the other hand, recent neuroimaging studies on severely brain-injured patients have developed neurobiologically-informed markers of conscious awareness that hold potential for improving monitoring of covert awareness during general anesthesia. Further research is required to determine the implementation of these assessments in the surgical context, and this approach provides promising avenues for improved detection of intraoperative awareness and prevention of accidental awareness under general anesthesia.