Neuromuscular complications of critical illness are common and can be severe and persistent in some patients. Neuromyopathy from critical illness and disuse atrophy from prolonged immobility contribute to muscle weakness acquired while in the intensive care unit. Although various risk factors (eg, severity of illness, corticosteroids, neuromuscular blocking agents) have been implicated in critical illness neuromyopathy (CINM), the evidence supporting these associations is inconsistent. Hyperglycemia may be an important risk factor for CINM, with tight glycemic control through intensive insulin therapy reducing the incidence of CINM. Early mobility in the intensive care unit may minimize disuse atrophy and possibly CINM, through exercise training and its anti-inflammatory effects. Although emerging data have demonstrated the safety, feasibility, and benefit of early mobility in critically ill patients, randomized controlled trials are needed to thoroughly evaluate its potential benefits on patients' muscle strength, physical function, and quality of life. Future studies are needed to elucidate the multiple mechanisms by which immobility, CINM, and other aspects of critical illness lead to muscle loss and neuromuscular dysfunction.