Patients with intensive care unit-acquired weakness have an increased risk of prolonged mechanical ventilation, which is a risk factor for prolonged stay and mortality. The most common cause of this problem is weakness of the diaphragm, which can derive from phrenic nerve injury associated with critical neuropathy, or with the complex multiorgan failure/systemic respiratory response syndrome causing muscle fiber lesion. Two conventional neurophysiological techniques are useful to investigate the respiratory muscles, phrenic nerve conduction, and needle electromyography of the accessory respiratory muscles and diaphragm. Phrenic nerve stimulation is a standard noninvasive technique; amplitude of the motor response can be reduced because of muscle fiber inexcitability or axonal loss. Electromyography of the diaphragm is an invasive method but is safe if performed as indicated. It can reveal neurogenic or myopathic motor units. Although these neurophysiological methods have limitations in the investigation of intensive care unit patients with severe respiratory involvement, normal phrenic nerve responses should exclude marked axonal loss and indicate a better prognosis.