<p>Transient or permanent cognitive changes among patients experiencing anesthesia, surgery, perioperative sleep disturbances, and the hospital environment in general have become an extensive topic of debate, particularly concerning older adults and individuals with pre-existing cognitive impairment. This narrative review advocates for an updated nomenclature and terminology in the classification of postoperative cognitive changes and summarizes the current understanding of the most important risk factors for postoperative delirium, focusing on patient-specific, anesthetic, and procedural aspects, including the impact of regional versus general anesthesia. Mounting evidence suggests that appropriate anesthetic depth as monitored by processed electroencephalogram (EEG) is important to preserve baseline postoperative cognitive function in vulnerable patients. The potential roles of cognitive prehabilitation, perioperative medications such as dexmedetomidine and antipsychotics, and early mobilization as well as maintenance of sleep quality for mitigating postoperative cognitive alterations are addressed to aid the practitioner in developing comprehensive care plans emphasizing brain health for this at-risk population. Current evidence highlights an urgent need for additional research in this domain of patient care. Targeted clinician education to understand the multifactorial and complex factors contributing to this perioperative conundrum is essential. Improvements in the prevention, monitoring, and treatment of postoperative cognitive alterations, especially in older adults with pre-existing cognitive conditions, remain an unmet need.</p>