Sedation is generally required during endotracheal intubation and mechanical ventilation in infants and children. While there are many options for the provision of sedation, the most commonly used agents such as midazolam and fentanyl demonstrate a context-sensitive half-life, which may result in a prolonged effect when these agents are discontinued following a continuous infusion. We present a 20-month-old infant who required endotracheal intubation due to respiratory failure following seizures. At the referring hospital, multiple laryngoscopies were performed with the potential for airway trauma. To maximize rapid awakening and optimize respiratory function surrounding tracheal extubation, sedation was transitioned from fentanyl and midazolam to remifentanil for 18–24 hours prior to tracheal extubation. The unique pharmacokinetics of remifentanil are presented in this study, its use in this clinical scenario is discussed, and its potential applications in the pediatric intensive care unit setting are reviewed.