Critical illness polyneuropathy (CIP) is common among patients in intensive care units (ICUs). However, it is rarely diagnosed in patients in most ICUs, because of the lack of knowledge, difficulties in clinical assessment, and failure to perform electrophysiologic studies. Nonetheless, CIP is a significant cause of difficulty in weaning patients from the ventilator and of long-term morbidity in survivors. Although no specific treatment is available, diagnosis is important for the institution of various nonspecific treatments and for prognosis. Moreover, research is important in arriving at a better understanding of the pathophysiologic mechanisms and, hence, possible avenues of specific treatment. Thus, this chapter emphasizes the nature of critical illness and the possible pathophysiology, the clinical and electrophysiologic features, and the differential diagnosis of CIP. Nonspecific and potential specific treatments are also discussed.