Survival from critical illness has improved in recent years, leading to increased attention to the sequelae of such illness. Neuromuscular weakness in the intensive care unit (ICU) is common, persistent, and has significant public health implications. The differential diagnosis of weakness in the ICU is extensive and includes critical illness neuromyopathy. Prolonged immobility and bedrest lead to catabolism and muscle atrophy, and are associated with critical illness neuromyopathy and ICU-acquired weakness. Early mobilization therapy has been advocated as a mechanism to prevent ICU-acquired weakness. Early mobilization is safe and feasible in most ICU patients, and improves outcomes. Implementation of early mobilization therapy requires changes in ICU culture, including decreased sedation and bedrest. Various technologies exist to increase compliance with early mobilization programs. Drugs targeting muscle pathways to decrease atrophy and muscle-wasting are in development. Additional research on early mobilization in the ICU is needed.