Hypoventilation can present as the primary manifestation or as a part of the clinical spectrum in a variety of diseases. It often goes unrecognized by clinicians and health care providers, especially if the presentation is subacute. If untreated, it is associated with increased morbidity and mortality. Some of the consequences of hypoventilation (e.g., cor pulmonale and pulmonary hypertension) may be irreversible. It becomes imperative that conditions commonly associated with hypoventilation (e.g., obesity hypoventilation syndrome, muscular dystrophy, and rigid chest wall diseases) be carefully evaluated and appropriate treatment implemented to prevent these complications. The ability to ventilate patients without invasive procedures is now available. These noninvasive therapies can be successfully implemented and are tolerated well by patients. The noninvasive positive pressure ventilation not only improves nocturnal hypoventilation during sleep but may improve muscle strength during the daytime. This review provides an overview of the treatment of hypoventilation in various diseases with emphasis on noninvasive positive pressure therapy. Treatment needs to be individualized to a given patient and the primary pathology. Success is impacted by the experience of the respiratory team caring for the patient.