SummaryObstructive sleep apnea (OSA) is characterised by recurring episodes of upper airway obstruction during sleep and the fundamental abnormality reflects the inability of the upper airway dilating muscles to withstand the negative forces generated within the upper airway during inspiration. Factors that result in narrowing of the oropharynx such as abnormal craniofacial anatomy, soft tissue accumulation in the neck, and rostral fluid shift in the recumbent position increase the collapsing forces within the airway. The counteracting forces of upper airway dilating muscles, especially the genioglossus, are negatively influenced by sleep onset, inadequacy of the genioglossus responsiveness, ventilatory instability, especially post arousal, and loop gain. OSA is frequently associated with comorbidities that include metabolic, cardiovascular, renal, pulmonary, and neuropsychiatric, and there is growing evidence of bidirectional relationships between OSA and comorbidity, especially for heart failure, metabolic syndrome, and stroke. A detailed understanding of the complex pathophysiology of OSA encourages the development of therapies targeted at pathophysiological endotypes and facilitates a move towards precision medicine as a potential alternative to continuous positive airway pressure therapy in selected patients.