Over the past decade, ketamine has emerged as a valuable addition to multimodal anesthesia (MMA). In light of the ongoing opioid crisis in the United States, which has resulted in thousands of deaths annually, and the recognition that postoperative analgesia remains a significant area for improvement, many anesthesiologists have sought to reevaluate analgesia and its practice in the perioperative setting. Postoperative pain is a rampant problem, often exacerbated by postoperative depression, sleep deprivation, and brain fog. The combination of anesthetics, including inhaled ethers, propofol, alpha-agonists, and other analgesics with ketamine, has morphed from subculture to mainstream practice. Yet, the new scientific underpinnings of this practice, derived from rapidly evolving neuroscience, are often left at the wayside by anesthesiologists. Nonetheless, the inclusion of ketamine into the toolbox of anesthesiologists and pain therapists is underway, notwithstanding great knowledge gaps that need to be addressed. This chapter tries to capitalize on four spheres, in which ketamine is likely to broaden our understanding of anesthesiology and the human mind in the future: (1) electroencephalogram (EEG) signatures of ketamine administration during MMA and sedation, (2) dreaming under anesthesia, (3) ketamine modulation of the cerebral glymphatic drainage system, and (4) the neuroscience of consciousness and unconsciousness.