Obesity, defined by a body mass index ≥30 kg/m2, has a major impact on respiratory health. Obesity-related chronic respiratory failure has become the primary cause for long-term home noninvasive mechanical ventilation although this condition remains often underdiagnosed. This chapter will focus on (1) the main pathophysiological mechanisms leading to obesity-related chronic respiratory failure and their implications for treatment decision, (2) the need to improve early diagnosis in these patients, and (3) treatment modalities, mainly use of long-term noninvasive positive airway pressure therapies. This chapter also addresses the importance of screening for comorbidities and the need to offer combined treatment strategies to improve long-term outcomes.