Hypoventilation in neuromuscular disease is attributed to both respiratory muscle weakness and reduced chemoreceptor sensitivity essential in ventilatory drive. Acute or chronic respiratory failure is seen in a spectrum of neuromuscular disease; whereas some are treatable others are progressive and devastating. Sleep is associated with a reduction in ventilation and hence worsening hypoventilation. Problems with sleep may be an early indicator of further muscle weakness and should prompt the clinician for further investigation, though usefulness of pulmonary function testing, arterial blood gas analysis, and other measures may not be universally predictive. The timing of respiratory failure is variable, but knowledge of the clinical aspects, pathogenesis, and treatment of respiratory failure and hypoventilation may be helpful in evaluating the patient with neuromuscular disease. For those with progressive and terminal disease, additional factors such as end of life care, especially ventilation and cough, may be useful for the patient, caregivers, and treating medical personnel.