A wide variety of mechanisms can lead to the hypoventilation associated with various medical disorders, including derangements in central ventilatory control, mechanical impediments to breathing, and abnormalities in gas exchange leading to increased dead space ventilation. The pathogenesis of hypercapnia in obesity hypoventilation syndrome remains somewhat obscure, although in many patients comorbid obstructive sleep apnea appears to play an important role. Hypoventilation in neurologic or neuromuscular disorders is primarily explained by weakness of respiratory muscles, although some central nervous system diseases may affect control of breathing. In other chest wall disorders, obstructive airways disease, and cystic fibrosis, much of the pathogenesis is explained by mechanical impediments to breathing, but an element of increased dead space ventilation also often occurs. Central alveolar hypoventilation syndrome involves a genetically determined defect in central respiratory control. Treatment in all of these disorders involves coordinated management of the primary disorder (when possible) and, increasingly, the use of noninvasive positive pressure ventilation.