Critical illness polyneuropathy (CIP) is a syndrome that was first extensively described in the early 1980s, mainly in patients with failure to wean from mechanical ventilation. The syndrome is further characterized by limb muscle weakness, usually more pronounced distally than proximally, and is often accompanied by atrophy. The facial musculature is often strikingly spared. Reduced or absent deep-tendon reflexes and loss of peripheral sensation to light touch and pin prick often accompany the syndrome. Involvement of the phrenic nerve has been shown to further contribute to delayed weaning from the ventilator in many patients. The electrophysiologic studies are consistent with a predominantly motor and, often to a lesser extent, sensory axonal polyneuropathy. The incidence of CIP is high, with often more than 50% of patients in major medical and surgical critical care units suffering from the syndrome. The systemic inflammatory response syndrome (SIRS) is strongly associated with CIP and, among the multiorgan failure often seen in SIRS, CIP is thought to represent a neurologic manifestation of SIRS. The neurologic effects of SIRS are thought to be mediated by released mediators like cytokines and free radicals, affecting the microcirculation of the central and peripheral nervous system. Examination of the peripheral nervous system is often unreliable, and the only way to establish a definitive diagnosis is by performing electrophysiologic studies. Morbidity and mortality rates are high. If the underlying problem causing sepsis and/or SIRS can be treated successfully, full recovery from CIP can occur. This recovery often occurs in a matter of weeks in milder cases and in months in more severe cases. Knowledge of CIP is essential for intensivists and other specialists who care for critically ill patients. This review summarizes the current available literature on this topic.