Delirium and poor sleep quality are common and often co-exist in hospitalized patients. A link between these disorders has been hypothesized but whether this link is a cause and effect relationship or simply an association resulting from shared mechanisms is yet to be determined. Potential shared mechanisms include: abnormalities of neurotransmitters, tissue ischemia, inflammation, and sedative exposure. Sedatives, while decreasing sleep latency, often cause a decrease in slow wave sleep and stage REM sleep and therefore may not provide the same restorative properties as natural sleep. Mechanical ventilation, an important cause of sleep disruption in ICU patients, may lead to sleep disruption not only from the discomfort of the endotracheal tube but also as a result of ineffective respiratory efforts and by inducing central apnea events if not properly adjusted for the patient’s physiologic needs. When possible, efforts should be made to optimize the patient-ventilator interaction to minimize sleep disruptions.