Rett syndrome (RTT) is a rare genetic disorder that can present challenges in airway management during general anesthesia. This is a case report involving a 23-year-old woman with RTT who received an intubated general anesthetic 3 times for dental treatment. The patient also had severe scoliosis, was bedridden, and had dysphagia. These contributing factors likely led to the development of postoperative respiratory complications including pneumonia after the first case. As a result, several changes were incorporated into the 2 subsequent anesthetic plans in efforts to reduce the risk of such complications. Despite these measures, the patient was suspected of having bronchitis postoperatively after the second anesthetic, although the third occurred uneventfully. Anesthetic management alterations included use of desflurane for anesthetic maintenance and postoperatively delaying oral intake and instituting active postural changes. © 2021 by the American Dental Society of Anesthesiology.