Chronic obstructive pulmonary disease (COPD) affects 6% of the general population and is the fourth-leading cause of death in the United States with severe and very severe disease accounting for 15% and 3% of physician diagnoses of COPD. Guidelines make few recommendations regarding providing the provision of care for the most severe stages of disease, namely Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III and IV with chronic respiratory failure. The effectiveness of inhaled drug therapy in very severe patients has not been assessed yet. Health care systems in many countries include public funding of long-term oxygen therapy for eligible candidates. Currently, there is little evidence for the use of mechanical ventilatory support in the routine management of hypercapnic patients. Pulmonary rehabilitation should be considered as a significant component of therapy, even in the most severe patients. Although Lung Volume Reduction Surgery has been shown to improve mortality, exercise capacity, and quality of life in selected patients, this modality is associated with significant morbidity and an early mortality rate in the most severe patients. Despite significant progress over the past 25 years, both short- and long-term outcomes remain significantly inferior for lung transplantation relative to other "solid" organ recipients. Nutritional assessment and management is an important therapeutic option in patients with chronic respiratory diseases. Morphine may significantly reduce dyspnoea and does not significantly accelerate death. No consistent improvement in dyspnoea over placebo has been shown with anxiolytics. Supplemental oxygen during exercise reduces exertional breathlessness and improves exercise tolerance of the hypoxaemic patient. Non-invasive ventilation has been used as a palliative treatment to reduce dyspnoea. Hypoxaemic COPD patients, on long-term oxygen therapy, may show reduced health-related quality of life, cognitive function, and depression. Only a small proportion of patients with severe COPD discuss end-of-life issues with their physicians.