Muscle wasting and paralysis are common complications in Intensive Care Unit (ICU) patients, where critical illness polyneuropathy (CIP) and critical illness myopathy (CIM), alone or in combination (CIP/CIM), are the commonest causes. CIP is an acute axonal sensory-motor polyneuropathy usually suspected in ICU patients who, after a period of days or weeks, cannot be weaned from the ventilator despite the absence of pulmonary or cardiac causes of respiratory failure, or because they suffer from various degrees of limb weakness. CIM is an acute primary myopathy with a continuum of myopathic findings, from myopathies with pure functional impairment and normal histology to myopathies with atrophy and necrosis. The true incidence of CIM is unknown, because neither the diagnosis of CIM nor the differential diagnosis between CIP and CIM in the ICU are easy, and requires specialized neurophysiological methods or biopsy investigations in addition to conventional nerve conduction studies and needle electromyography. When these methods are used, CIM is as frequent as or more frequent than CIP. Failed weaning of patients from the ventilator, inappropriate evaluations of comatose patients and prolonged disability after ICU discharge are common consequences of CIP/CIM. Recent data indicate that CIM has a better prognosis than CIP, and differential diagnosis is therefore important to predict long term outcome in ICU patients. Bioenergetic failure is thought to be a relevant pathophysiological mechanism explaining both CIP/CIM and multi-organ failure. Indeed, CIP/CIM itself should be considered as the failure of the peripheral nervous-muscular system.