This chapter addresses the use of long-term non-invasive positive pressure ventilation (NIPPV) (to the exclusion of continuous positive airway pressure) in the different clinical settings in which it is currently proposed: principally in diseases responsible for hypoventilation characterized by elevated PaCO2. Nasal masks are predominantly used, followed by nasal pillow and facial masks. Mouthpieces are essentially indicated in case daytime ventilation is needed. Many clinicians currently prefer pressure-preset ventilator in assist mode as the first choice for the majority of the patients with the view of offering better synchronization. Nevertheless, assist-control mode with volume-preset ventilator is also efficient. The settings of the ventilator must insure adequate ventilation assessed by continuous nocturnal records of at least oxygen saturation of haemoglobin-measured by pulse oximetry. The main categories of relevant diseases include different types of neuromuscular disorders, chest-wall deformities and even lung diseases. Depending on the underlying diseases and on individual cases, two schematic situations may be individualized. Either intermittent positive pressure ventilation (IPPV) is continuously mandatory to avoid death in the case of complete or quasi-complete paralysis or is used every day for several hours, typically during sleep, producing enough improvement to allow free time during the daylight in spontaneous breathing while hypoventilation and related symptoms are improved. In case of complete or quasi-complete need of mechanical assistance, a tracheostomy may become an alternative to non-invasive access. In neuromuscular diseases, in kyphosis and in sequela of tuberculosis patients, NIPPV always significantly increases survival. Conversely, no data support a positive effect on survival in chronic obstructive pulmonary disease.