OBJECTIVES/HYPOTHESIS: Drug-induced sleep endoscopy (DISE) is used to determine surgical therapy for obstructive sleep apnea (OSA); however, the effects of anesthesia on the upper airway are poorly understood. Our aim was to systematically review existing literature on the effects of anesthetic agents on the upper airway. DATA SOURCES: PubMed, CINAHL, EBM reviews and Scopus (all indexed years). REVIEW METHODS: Inclusion criteria included English language articles containing original human data. Two investigators independently reviewed all articles for outcomes related to upper airway morphology, dynamics, neuromuscular response, and respiratory control. RESULTS: The initial search yielded 180 abstracts; 56 articles were ultimately included (total population = 8,540). The anesthetic agents studied were: topical lidocaine, propofol, dexmedetomidine, midazolam, pentobarbital, sevoflurane, desflurane, ketamine, and opioids. Outcome measures were diverse and included imaging studies, genioglossus electromyography, endoscopic airway assessment, polysomnography, upper airway closing pressure, and clinical evidence of obstruction. All agents caused some degrees of airway collapse. Dexmedetomidine did not have dose-dependent effects when evaluated using cine magnetic resonance imaging, unlike sevoflurane, isoflurane, and propofol, and caused less dynamic collapse than propofol. CONCLUSIONS: Studies assessing the effect of anesthesia on the upper airway in patients with and without OSA are limited, and few compare effects between agents. Medications with minimal effect on respiratory control (e.g., dexmedetomidine) may work best for DISE. Laryngoscope, 2015