Obstructive sleep apnea (OSA) is a common sleep disorder with serious associated morbidities. Although several treatment options are currently available, variable efficacy and adherence result in many patients either not being treated or receiving inadequate treatment long term. Personalized treatment based on relevant patient characteristics may improve adherence to treatment and long-term clinical outcomes. Four key traits of upper airway anatomy and neuromuscular control interact to varying degrees within individuals to cause OSA. These are: (1) the pharyngeal critical closing pressure, (2) the stability of ventilator chemoreflex feedback control (loop gain), (3) the negative intraesophageal pressure that triggers arousal (arousal threshold), and (4) the level of stimulus required to activated upper airway dilator muscles (upper airway recruitment threshold). Simplified diagnostic methods are being developed to assess these pathophysiological traits, potentially allowing prediction of which treatment would best suit each patient. In contrast to current practice of using various treatment modes alone, model predictions and pilot clinical trials show improved outcomes by combining several treatments targeted to each patient's pathophysiology profile. These developments could theoretically improve efficacy and adherence to treatment and in turn reduce the social and economic health burden of OSA and the associated life-threatening morbidities. This article reviews OSA pathophysiology and identifies currently available and investigational treatments that may be combined in the future to optimize therapy based on individual profiles of key patient pathophysiological traits.