Delirium has been consistently identified as a risk factor for critical illness brain injury, but ICU patients are exposed to a multitude of risk factors for delirium and it remains unclear which of these risk factors should be targeted to improve long-term cognitive outcomes. Because exposure to sedating medications—which are frequently used to treat unwanted yet common symptoms during critical illness—is a risk factor for delirium that is directly controlled by clinicians, the relationship between sedation, delirium, and long-term cognition is of great interest to clinicians, researchers, and patients. This review describes theoretic relationships between sedation, delirium, and long-term cognition and reviews the evidence supporting these theoretic relationships.