Down syndrome, or trisomy 21, is the most common chromosomal anomaly in children born alive. It presents with distinct clinical and facial features and is related to various medical challenges, including otolaryngological issues and obstructive sleep apnea. Otolaryngological problems such as stenotic ear canals, chronic ear disease, internal auditory canal and cochlear nerve hypoplasia, laryngomalacia, and subglottic stenosis predispose to a high incidence of cerumen impaction, middle ear effusion, acute otitis media with effusion, and conductive, sensorineural, or mixed hearing loss in Down syndrome patients. Due to the multiple problems related to otolaryngology, it is crucial to perform frequent evaluations, even at birth, including otoscopy, brainstem auditory testing, and tympanometry. Furthermore, obstructive sleep apnea can be diagnosed with polysomnography, and adenotonsillectomy can be considered as an optimal treatment.