Generalized muscle weakness in critically ill patients can result in prolonged periods of artificial ventilation and longer stays in the intensive care unit. Both neuropathic (critical illness polyneuropathy) and myopathic (critical illness myopathy) abnormalities seem to play an important role for this prolonged weakness. This article reviews its complex differential diagnosis with special emphasis on the current understanding of the neuromuscular syndromes. An efficient diagnostic plan is necessary for the exclusion of other curable causes of prolonged muscle weakness even in the presence of polyneuromyopathic changes. Psychological support of the patient and prophylaxis of secondary complications of prolonged immobilization are crucial when specific therapy is not possible.