Fatigue is a common complaint in people living with physical disabilities. This issue of the North America Clinics of Physical Medicine and Rehabilitation is devoted to this important topic. Subjects covered include the physiology, assessment, presentation and treatment of fatigue in adults with various disorders such as multiple sclerosis, spinal cord injury, traumatic brain injury, acquired brain injury, rheumatological disorders, cardiopulmonary disorders and neuromuscular disease. Additional topics covered include neuroimaging of fatigue and fatigue in children.