The neuromuscular syndrome of acute limb and respiratory weakness that commonly accompanies patients with multi-organ failure and sepsis constitutes critical illness polyneuropathy. It is a major cause of difficulty in weaning off the patient from the ventilator after respiratory and cardiac causes have been excluded. It is usually an axonal motor-sensory polyneuropathy, and is usually associated with or accompanied with a coma producing septic encephalopathy. The neuropathy is usually not apparent until the patient′s encephalopathy has peaked, and may be noted only when the brain dysfunction is resolving. Patients usually have a protracted hospital course complicated by multi-organ failure and the systemic inflammatory response syndrome. Elevated serum glucose levels and reduced albumin are risk factors for nerve dysfunction, as is prolonged intensive care unit stay. Polyneuropathy may develop after only one week of the systemic inflammatory response syndrome, but the frequency tends to correlate with the duration of the severe illness.