Pediatric obstructive sleep apnea (OSA) affects 3-5% of the general pediatric population in the United States. However, in specific populations, the prevalence can be much higher. For example, in cerebral palsy the prevalence is over 50%, and in Trisomy 21, nearly all patients are diagnosed with OSA during their lifetimes. In otherwise healthy children, adenotonsillectomy is curative in approximately 70% of patients, but in patients with particular diseases and syndromes, the management is more complex and often requires both medical and surgical interventions. In Trisomy 21, adenotonsillectomy results in a 51% decrease in the average apnea-hypopnea index. Simultaneously, these children have a 33% prevalence of periodic limb movement disorders, potentially impacting their sleep quality. When managing special populations with OSA, care should be taken to ensure that other aspects of the patient’s medical condition are considered. The goals of this panel discussion are to introduce the otolaryngologist to special considerations for managing pediatric OSA in patients with complex diseases and syndromes, and help them determine when referral to specialty care, including sleep medicine and neurology, would be indicated before considering surgery. This panel will discuss key concepts in approaching OSA within the context of a pediatric patient with the particular conditions of Trisomy 21, cerebral palsy, mucopolysaccharidoses, autism, epilepsy, and other genetic syndromes, focusing on 1) surgical OSA management beyond adenotonsillectomy, 2) concomitant non-obstructive sleep disorders that often affect these patients, and 3) factors relating to the underlying disease processes that can impact clinical sequelae associated with OSA. These concepts will be illustrated using high-quality studies from otolaryngology, as well as other specialties.