A significant portion of critical care patients experience delirium. This form of acute brain dysfunction is associated with increased hospital stay, increased mortality, and greater long-term cognitive deficits. Critical care nurses are on the frontline with these patients and can make a significant impact on patient outcomes, including reducing the negative outcomes and experience of delirium. It is, therefore, imperative that nurses be equipped with a solid knowledge base of understanding delirium, which includes what has been reported specifically unique to delirium in the intensive care unit. This article will provide an overview of delirium and describe an interdisciplinary model of care combining multiple evidence-based practice strategies that nurses can and should use to help systematically reduce modifiable delirium risk factors. In addition, this article will provide an overview of recent reports concerning pharmacologic management of delirium in the intensive care unit.