Positive airway pressure (PAP) therapy is the first-line treatment for obesity hypoventilation syndrome (OHS), which characterized by daytime hypercapnia (PaCO2>45mmHg) in obese people (BMI>30kg/m2) who experiences hypoventilation. Alveolar hypoventilation is a result of an imbalance between the capability of respiratory muscles to maintain ventilation and gas exchange leading to daytime hypercapnia that can be assessed by blood gas analysis. In patient with OHS, the presence of daytime hypercapnia is explained by several co-existing mechanisms such as obesity-related changes in the respiratory system, alterations in respiratory drive and breathing abnormalities during sleep. Polysomnography is recommended to exclude concomitant obstructive sleep apnea (OSA). The clinical symptoms of hypoventilation are used to evaluate the disease severity and prognosis as well as decision-making for initiating PAP. Treatment options include continuous positive airway pressure (CPAP), bi-level PAP and other non-invasive ventilation (NIV) modalities. The current recommendation is to use CPAP rather than NIV if concomitant severe OSA in stable patients. NIV can be beneficial in patients having hypercapnia in the absence of significant apnea, if the patient did not tolerate PAP or did not respond to CPAP as initial therapy. Application of PAP in OHS shown benefits, which include improve daytime sleepiness, significantly reduce daytime hypercapnia, increase in the ventilatory response, improve lung compliance and quality of life. However, NIV should be used in hospitalized patients with acute hypercapnia respiratory failure suspected of having OHS until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory. The lecture will evaluate PAP therapy and ventilatory strategies in the management of OHS using latest clinical evidences.