Exercise training is an essential component of pulmonary rehabilitation and is associated with improved function and other important outcomes in persons with chronic lung disease. A subset of pulmonary rehabilitation patients experience hypoxemia that may occur or worsen with exercise. For the purpose of this review, severe exercise-induced hypoxemia is defined as an S(pO(2)) of < 89% during exercise, despite use of supplemental oxygen delivered at up to 6 L/min. There is a paucity of evidence and clinical guidelines that address assessment and management of this important manifestation of chronic lung disease. This review presents background of this topic and suggests strategies for assessment, management, and safety measures for patients with severe exercise-induced hypoxemia.