Oxygen therapy is useful in the treatment of COPD since the 1970s because of the positive impact on mortality and morbidity of home use of oxygen. Long-term oxygen therapy (LTOT) has become widely accepted in the last 30 years in selected, continuously hypoxemic patients based on two milestone studies. On the other hand, when hypoxemia is intermittent (i.e., associated with exercise, sleep, or eating), the use of oxygen remains an area of debate for physicians. Despite extensive work by many investigators that has helped our understanding of the mechanisms believed to be responsible for intermittent hypoxemia, the therapeutic benefits of supplemental oxygen in this setting remain needs trials. LTOT is essential for patients with a PaO2 of less than 55 mm Hg, PaO2 < 59 mm Hg with evidence of polycythemia, or cor pulmonale. Many patients with COPD who are not hypoxemic at rest worsen during exertion. Dose of oxygen is 1-2 L per minute. During exercise or sleep, increase oxygen 0.5 L per minute. Primary goal is to increase the baseline PaO2 to at least 60 mmHg (90% SaO2). Reevaluate these patients 1-3 months after initiating therapy because some patients may not require long-term oxygen.