OBJECTIVE: To review of the natural history of airway disease in children with muccopolysaccharidoses (MPSs), which represent a group of hereditary progressive disorders caused by excessive accumulation of glycosaminoglycans in various tissues. DESIGN: Retrospective medical chart review. SETTING: Tertiary referral academic medical center. PATIENTS: Twenty-seven children with MPSs. MAIN OUTCOME MEASURES: A review of the medical charts of 27 children with MPSs between February 1, 1984, and February 1, 2004, was performed to examine the natural history of airway disease. RESULTS: Clinically upper airway obstruction was noted in 19 patients (70%) and necessitated a tracheotomy in 3 patients (11%). Fourteen of the 27 patients underwent bone marrow transplantation, and successful engraftment resulted in a significant decrease in obstructive symptoms in 13 of the 14 patients. CONCLUSIONS: Patients affected by MPSs require the vigilant attention of the otolaryngologist, as sleep apnea and upper airway obstruction are common complications. Successful bone marrow engraftment may alter the natural history of airway disease and result in substantial improvement in symptomatic airway disease in children with MPSs.