Observational studies of patients receiving prolonged mechanical ventilation and other forms of critical care support have determined acquired neuromuscular disorders to be extremely common. Early studies used electrophysiologic investigations to diagnose critical illness polyneuropathy (CIP) and muscle biopsy to confirm critical illness myopathy (CIM). More recent approaches seek to obviate these invasive techniques and build on a standardized bedside neuromuscular examination to identify patients with acquired weakness syndromes. Serial examination in the alert patient may serve as a reasonable prognosticator for most patients. The importance of ICU-acquired weakness syndromes is supported by the observation that muscle wasting and weakness are among the most prominent long-term complications of survivors of ARDS. In addition, a strong association appears to exist between acquired weakness and protracted ventilator dependence, an important determinant of ICU length of stay. Multivariate analysis has identified several risk factors associated with increased incidence for ICU-acquired weakness, including severe systemic inflammation, medications (specifically, corticosteroids and neuromuscular blocking agents), glycemic control, and immobility. We advocate an approach to this common syndrome that identifies risk factors early in the hope of minimizing their impact.