Neuromuscular diseases cause many changes that affect ventilation and ventilatory control. The pattern of ventilation may become abnormal because of muscle disease. Muscle fatigue and discordant breathing can lead to hypoventilation and CO2 retention. Motoneuron destructive and demyelinating disorders inevitably lead to hypoventilation and hypercapnia. Changes in chest wall mechanics can lead to changes in level of ventilation and ventilatory drive. In many neuromuscular disorders, ventilatory response to CO2 is depressed, but this does not imply an abnormal central control mechanism in all instances. Many patients with neuromuscular diseases have a normal ventilatory drive as manifested by a normal P0.1 but have low ventilation because of abnormalities in muscle function and neuromuscular transmission. Central drive is diminished in some patients with neuromuscular disease but not in the majority of cases. Hypoventilation during sleep is a common problem in neuromuscular diseases. Thus, a combination of factors can lead to abnormal patterns of breathing and hypoventilation in these disorders; no single pathophysiologic mechanism can explain all the abnormalities. Clinically, it is important to appreciate the prevalence of ventilatory control disorders and include appropriate evaluations when assessing patients with neuromuscular diseases and offering therapeutic options.