Bed rest is a common intervention for critically ill adults. Associated with both benefits and adverse effects, bed rest is undergoing increasing scrutiny as a therapeutic option in the intensive care unit. Bed rest has molecular and systemic effects, ultimately affecting functional outcomes in healthy individuals as well as in those with acute and critical illnesses. Using empirical sources, the purpose of this article was to describe the consequences of bed rest and immobility, especially consequences with implications for critically ill adults in the intensive care unit. This review uses body systems to cluster classic and current results of bed rest studies, beginning with cardiovascular and including pulmonary, renal, skin, nervous, immune, gastrointestinal/metabolic, and skeletal systems. It concludes with effects on muscles, a system profoundly affected by immobility and bed rest.