Delirium is a common pathologic event in both medical and surgical patients. It is essential to note that patients who develop delirium have worse long term outcomes. The etiology and pathogenesis of delirium are extremely complex and not entirely understood. Certain medications classes are implicated in delirium. For example, medications targeting muscarinic acetylcholine receptors are well known to be associated with delirium and altered mentation. Propofol is a medication commonly used in anesthesiology practice and sedation in intubated patients. In vitro studies provided evidence that propofol actively interacts with muscarinic acetylcholine receptors. Additionally, some, but not all clinical studies demonstrated that propofol led to delirium. Therefore, future prospective studies investigating the use of propofol and delirium occurrence are of paramount importance. These studies should adjust for such common confounders as patients' demographics and age, comorbid conditions, use of other medications, type of surgery, baseline cognitive status, etc. Another important task would be to research the susceptibility for propofol-related delirium. By studying these critical questions, we will gain additional insights into the complex etiology and pathobiology of delirium in addition to a better understanding of the pharmacology of propofol.