The differential diagnosis of generalized weakness in ICU patients is quite broad. Although neuromuscular disorders are the most common causes of generalized weakness, a thorough evaluation is necessary to delineate the underlying cause of weakness. Biochemical studies, neuroimaging, and electrophysiologic studies help to delineate most of the common disorders associated with weakness. Prompt identification of a neurologic disorder and initiation of therapy speeds up recovery and reduces morbidity and mortality in these patients.