Obesity is of growing concern all over the world since > 312 millions of individuals have a body mass index > 30 kg/m2. Respiratory consequences of obesity are now of major concern in the pulmonary specialty, including asthma, obstructive sleep apnea syndrome (OSAS), obesity-hypoventilation syndrome (OHS), and some acute situations like hypercapnic respiratory failure and respiratory postsurgical complications. OHS is commonly defined as the association of obesity with daytime hypercapnia (Paco2 > 45 mm Hg) in the absence of any other respiratory disease. OHS is one of the many etiologies of chronic respiratory failure and has become a frequent indication to initiate long-term noninvasive mechanical ventilation (NIV) in most European countries.1– Nocturnal NIV has been shown to be clinically effective in OHS because of a rapid and sustained improvement of daytime arterial blood gas levels2 and a net reduction of daytime sleepiness. However, mechanisms of improvement under NIV remain unclear, as well as the physiopathology and the natural history of the disease.