Neuromuscular disorders are increasingly recognized as a cause of both short- and long-term physical morbidity in survivors of critical illness. This recognition has given rise to research aimed at better understanding the risk factors and mechanisms associated with neuromuscular dysfunction and physical impairment associated with critical illness, as well as possible interventions to prevent or treat these issues. Among potential risk factors, bed rest is an important modifiable risk factor. Early mobilization and rehabilitation of patients who are critically ill may help prevent or mitigate the sequelae of bed rest and improve patient outcomes. Research studies and quality improvement projects have demonstrated that early mobilization and rehabilitation are safe and feasible in patients who are critically ill, with potential benefits including improved physical functioning and decreased duration of mechanical ventilation, intensive care, and hospital stay. Despite these findings, early mobilization and rehabilitation are still uncommon in routine clinical practice, with many perceived barriers. This review summarizes potential risk factors for neuromuscular dysfunction and physical impairment associated with critical illness, highlights the potential role of early mobilization and rehabilitation in improving patient outcomes, and discusses some of the commonly perceived barriers to early mobilization and strategies for overcoming them.