The key role of noninvasive positive pressure ventilation (NPPV) is well documented in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) since it may avoid endotrachal intubation in >50% of cases when used as the initial treatment. However, currently only minimal data is available to assess usefulness of NPPV in COPD patients on a long-term basis. Even if such studies are difficult to manage, there is clearly a need for prospective studies comparing long-term oxygen therapy (LTOT) and NPPV in the most severe COPD in a large amount of patients and on a real long-term basis of several years. Two randomized prospective studies are being completed in Europe and the first preliminary results show that NPPV is associated with a reduction of hospitalization for chronic respiratory failure decompensation. The main beneficial effect of long-term mechanical ventilation in COPD patients with chronic respiratory failure implies a correction of nocturnal hypoventilation that could persist beyond the ventilation period because of a temporary improvement in carbon dioxide sensitivity that is often blunted in these patients. A synthesis from the literature suggest to consider NPPV for severe COPD patients who present with chronic hypoxia and hypercapnia and develop an unstable respiratory condition. Instability may be appreciated on a clinical basis and confirmed by a progressive worsening of arterial blood gas tensions, leading to frequent cardiorespiratory decompensations with ominous ARF episodes. NPPV should also be considered after an ARF episode successfully treated by noninvasive ventilation but with the impossibility to wean the patient from the ventilator. Thus, noninvasive positive pressure ventilation could be proposed as a preventive treatment in severe chronic obstructive pulmonary disease patients with unstable respiratory condition associated with fluctuating hypercapnia before, during and after an acute respiratory failure episode, avoiding the need for a tracheotomy. Adjunction of noninvasive ventilation to exercise rehabilitation is under evaluation.