Amal M Osman,1,2 Sophie G Carter,1,2 Jayne C Carberry,1,2 Danny J Eckert1,2 1Neuroscience Research Australia (NeuRA), 2School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia Abstract: The prevalence of obstructive sleep apnea (OSA) continues to rise. So too do the health, safety, and economic consequences. On an individual level, the causes and consequences of OSA can vary substantially between patients. In recent years, four key contributors to OSA pathogenesis or “phenotypes” have been characterized. These include a narrow, crowded, or collapsible upper airway “anatomical compromise” and “non-anatomical” contributors such as ineffective pharyngeal dilator muscle function during sleep, a low threshold for arousal to airway narrowing during sleep, and unstable control of breathing (high loop gain). Each of these phenotypes is a target for therapy. This review summarizes the latest knowledge on the different contributors to OSA with a focus on measurement techniques including emerging clinical tools designed to facilitate translation of new cause-driven targeted approaches to treat OSA. The potential for some of the specific pathophysiological causes of OSA to drive some of the key symptoms and consequences of OSA is also highlighted. Keywords: pathophysiology, sleep-disordered breathing, arousal, upper airway physiology, control of breathing, precision medicine