Respiratory muscle fatigue is induced experimentally by adding high external resistances to breathing. The role played by respiratory muscle fatigue in exercise limitation and in acute respiratory failure is still unclear. The electromyogram often reflects contractions beyond the fatigue threshold, but overt force failure has been only rarely demonstrated under these circumstances. Hypercapnic ventilatory failure may possibly not result from fatigue, but rather from an adaptation of the respiratory system for avoiding fatigue. The treatment of fatigue comprises respiratory muscle support by adequate nutrition and oxygen delivery, and if needed respiratory muscle rest by mechanical ventilation.