Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurring collapse of the pharyngeal airway leading to restricted airflow. OSA is becoming increasingly common with at least moderate disease now evident in 17% of middle aged men and 9% of women. The list of recognized adverse health consequences associated with OSA is growing and includes daytime symptoms of sleepiness, impaired cognition and risk of motor vehicle accidents as well as associations with hypertension, cardiovascular morbidity, malignancy and all-cause mortality. In this context adequate treatment of OSA is imperative; however, there are well-recognized pitfalls in the uptake and usage of the standard treatment modality, Continuous Positive Airway Pressure (CPAP). A broad range of pathophysiological mechanisms are now recognized beyond an anatomically smaller pharyngeal airway and impaired compensatory pharyngeal muscle responsiveness. Perturbations in ventilatory control stability, low arousal threshold, sleep-related decrease in lung volume and fluid redistribution as well as upper airway surface tension have all been shown to variously contribute to sleepdisordered breathing. Many new therapies are emerging from these advances in understanding of the mechanisms of OSA. Although many may not be universally effective, the promise of phenotyping patients according to their individual pathophysiology in order to target one or more therapies may prove highly effective and allow the treatment of OSA towards a personalized medicine approach.