When pediatric patients require mechanical ventilation in the emergency department, the emergency clinician should be prepared to select initial ventilator settings and respond to an intubated patient's dynamic physiologic needs to ensure ongoing oxygenation, ventilation, and hemodynamic stability. Pressure-targeted ventilation is generally recommended in pediatric patients, with initial ventilator settings varying depending on age and the etiology of respiratory failure. This issue reviews indications for mechanical ventilation and offers recommendations for ventilator settings and dosing of analgesics, sedatives, and neuromuscular blockers, with a focus on patient populations in whom the approach to mechanical ventilation may be different.