Extubation failure, defined as the need for reinstitution of ventilatory support within 24 to 72 hours of planned endotracheal tube removal, occurs in 2 to 25% of extubated patients. The pathophysiologic causes of extubation failure include an imbalance between respiratory muscle capacity and work of breathing, upper airway obstruction, excess respiratory secretions, inadequate cough, encephalopathy, and cardiac dysfunction. Compared with patients who tolerate extubation, those who require reintubation have a higher incidence of hospital mortality, increased length of ICU and hospital stay, prolonged duration of mechanical ventilation, higher hospital costs, and an increased need for tracheostomy. Given the lack of proven treatments for extubation failure, clinicians must be aware of the factors that predict extubation outcome to improve clinical decision making. Risk factors for extubation failure include being a medical, multidisciplinary, or pediatric patient; age greater than 70 years; a longer duration of mechanical ventilation; continuous intravenous sedation; and anemia. Tests designed to assess for upper airway obstruction, secretion volume, and the effectiveness of cough can help to improve prediction of extubation failure. Rapid reinstitution of ventilatory support in patients who fail extubation may improve outcome.