The sleep state is associated with significant changes in respiratory physiology, including ventilatory responses to hypoxia and hypercapnia, upper airway and intercostal muscle tone, and tidal volume and minute ventilation. These changes are further magnified in certain disease states, such as chronic obstructive pulmonary disease, restrictive respiratory disorders, neuromuscular conditions, and cardiac diseases. This article discusses the regulation of breathing during sleep in health and associated comorbid conditions.