Respiratory failure accounts for the majority of deaths in amyotrophic lateral sclerosis (ALS) but only rarely is ALS diagnosed on the basis of respiratory insufficiency. We report four ALS patients presenting with acute respiratory failure. In three patients we have performed EMG needle examination of both hemidiaphragms which showed severe denervation. We reviewed 25 patients previously described presenting with respiratory failure. Almost all patients showed upper limbs weakness and diaphragm involvement; few patients had bulbar dysfunction. The prognosis of these patients is not always in permanent ventilator dependence. Rapidly progressive ventilatory failure may be a striking initial sign of ALS; the main reason is a weakened diaphragm. There are possibilities of significant improvement after a period of rest with ventilatory assistance. In the initial phase of the disease, bulbar dysfunction is not the more common reason of acute respiratory failure.