Primary mitochondrial cytopathies include more than 40 different identified diseases that have varied genetic features. The common factor among these diseases is that the mitochondria are unable to effectively complete oxidative phosphorylation to generate energy. One in 5000 children per year in the United Sates are born with mitochondrial disease. The term primary mitochondrial disease refers specifically to mitochondrial dysfunction caused by genetic mutations directly impacting the composition and function of the respiratory chain. These defects impair mitochondrial oxidative phosphorylation, the process by which oxidation of the end products of metabolism in the electron transport chain is coupled to phosphorylation of adenosine diphosphate to produce energy in the form of adenosine triphosphate. The effects of mitochondrial disease can be quite varied, and the severity of the defect may be great or small. We sought to find the common otolaryngologic manifestations of this disease, to enable better treatment of the patients. We report on 41 pediatric cases of mitochondrial cytopathy diagnosed from 2001 to 2006 at our Center for Child Neurology (Cleveland, OH). We performed a retrospective review after obtaining institutional review board approval. Patients who had otologic manifestations including recurrent otitis media and hearing loss comprise 14.6%. Patients who were noted to have obstructive sleep apnea requiring adenotonsillectomy comprise 9.8%. Patients who had dysphagia comprise 22%; however, all of these patients were noted to have some developmental delay and seizures. It was also noted that there was a 17% incidence of gastroesophageal reflux, and 36.6% incidence of seizures in our patient population. In conclusion, mitochondrial cytopathies exhibit extreme clinical variability. This variability greatly increases the burden for affected families and impairs our ability to understand the pathogenesis of these disorders. In otolaryngologic examination, children appear to have recurrent otitis, dysphagia, and sleep apnea, at a much higher incidence than the general pediatric population. A comprehensive management approach to these patients including pediatric neurology, genetics, speech pathology, otolaryngology, and audiology is essential to their care.