OSA is associated with significant adverse outcomes with far-reaching health-care implications. OSA is much more common and severe in patients with Down syndrome (DS) than in the general population, yet there is a striking lack of literature in this area. In this review article, we have summarized the current state of knowledge and presented the available data on OSA in DS. The higher prevalence and severity of OSA in patients with DS may be related to unique upper airway anatomic features as well as increased risk for obesity, hypothyroidism, gastroesophageal reflux disease, and generalized hypotonia. Although many of the manifestations of OSA in patients with DS are similar to those seen in the general population, the relative morbidity is significantly higher. For individuals with DS who already face cognitive challenges, the added impact of OSA on cognitive function may hinder their ability to function independently and reach their full potential. Screening and evaluation for OSA should be done in children and adults with DS. Treatment of OSA in DS involves the use of CPAP, upper airway surgery, and dental appliances, along with weight-reduction strategies, nasal steroids, and oral leukotriene modifiers as adjunctive treatments. The treatment plan should be individualized for each patient with DS, taking into account age, comorbid conditions, and barriers to treatment adherence. Future research should aim to better characterize OSA, further evaluate neurocognitive outcomes, and evaluate the efficacy of treatments in patients with DS.