The pathophysiology of Obstructive Sleep Apnoea (OSA) involves acomplex interaction of structural and functional factors that result inupper airway collapse during sleep. Moreover, there is considerablevariation in contributing factors between individuals. An abnormalanatomical substrate is a key factor in the development of OSA.Craniofacial abnormalities, enlargement of upper airway soft tissuestructures, central obesity, and an excess of regional adipose tissueare known anatomic risk factors for OSA. Although obesity is generallyconsidered the major attributing risk factor for OSA, craniofacialmorphology is increasingly recognised as an important interacting factorin OSA pathogenesis. It is well established from studies using imagingtechniques that craniofacial abnormalities are common in patients withOSA. Mandibular retrusion, maxillary deficiency, inferior displacementof the hyoid bone and cranial base abnormalities are amongst themost commonly reported findings. Sleep-related changes in upperairway dilator muscle activity are also important, and inter-individualvariability in the degree of neuromuscular compensation has beennoted. The basis for this variability may relate to neuropathy of upperairway muscles, impaired muscle function or defects in mechanicalcoupling. Ventilatory control instability and impaired arousal responsesappear to play a role in perpetuating respiratory events. More recently,additional factors such as airway surface tension and rostral fluid shiftsin the recumbent position have been implicated to play a role in thepathophysiology of OSA.CPAP remains the treatment of choice for OSA, acting as a pneumaticsplint that overcomes the pathophysiological factors, regardlessof their relative contributions. However, issues with suboptimalcompliance have driven the quest for alternative treatments. Suchalternatives include oral appliance therapy, nasal valves producingexpiratory positive airway pressure, oral exercises, and novel surgicalapproaches (including hypoglossal nerve stimulation). Advances inour understanding of OSA pathophysiology, coupled with therapeuticinnovations point to the need for a more personalised approach to thediagnosis and management of OSA. Such an approach requires morecomprehensive characterisation of specific contributing factors at theindividual patient level (“phenotyping”), forming the basis of a tailoredapproach to management. Innovative and cost-effective phenotypingtechniques that can be easily implemented in clinical care are needed to realise the vision of personalised medicine for our field.