Neuromuscular disorders cause respiratory failure when they significantly impair the respiratory muscle pump. This is a complex system involving the diaphragm, intercostal, neck, shoulder girdle, abdominal wall and possibly paraspinal muscles. The dilator muscles of the palate, pharynx and larynx maintain a patent airway and air conduit. The diaphragm is the main muscle of inspiration, but is aided by the parasternal intercostals, and additionally by the accessory respiratory muscles in forceful inspiration, diaphragmatic weakness or compromised diaphragmatic function as is the case in lung emphysema. Exhalation is passive, but forceful expiration and cough require the abdominal wall and a portion of the intercostals. This chapter focuses on the physiology of the muscles involved in respiration, and the recognition of developing neuromuscular respiratory failure, its clinical evaluation and assessment, and basic principles of management.