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For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neurocognitive dysfunction at different times after cardiac surgery, ranging from “postoperative delirium” to “postoperative cognitive dysfunction or decline.” Delirium is a clinical diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Postoperative cognitive dysfunction is not included in the DSM-5 and has been heterogeneously defined, though a recent international nomenclature effort has proposed standardized definitions for it. Here, the authors discuss pathophysiologic mechanisms that may underlie these complications, review the literature on methods to prevent them, and discuss novel approaches to understand their etiology that may lead to novel treatment strategies. Future studies should measure both delirium and postoperative cognitive dysfunction to help clarify the relationship between these important postoperative complications.