This book is a comprehensive summary of the recommendations for best practice, and current evidence, for physical activity and rehabilitation of functional deficits in individuals with end-stage diseases. While advances in technology have afforded us the opportunity to live longer lives, it has also demanded an expansion of focus of medical interventions towards palliative care to enhance the quality of life. Exercise and healthcare professionals must strive to broaden their perspectives to provide for the unique needs of these individuals, and to successfully engage with them, to achieve the most positive outcomes throughout the entire continuum of care. Healthcare providers play a critical role in advocating for care to allow individuals to remain physically active for as long as possible, even in the face of declining health. Finally, due to the increasing and progressively emergent healthcare utilization required by these individuals, a significant cost burden is experienced by healthcare systems, patients, families, and payers. There is evidence of substantial protective effects of physical activity, prevention, safety, and rehabilitative procedures to reduce hospital readmissions, reduce length of stay, and assist in avoiding unwarranted or unnecessary diagnostic tests or procedures. Physical activity has been proven to have a substantial impact and protective effects on virtually all medical conditions. During curative management, but especially during transitional phases to palliative care, other strategies need enhanced consideration to complement the existing plan of care and help to improve patient’s quality of life. Ideally, physical medicine would be at the forefront of allowing individuals to live their best life until the very end. Physical Activity and Rehabilitation in Life-threatening Illness is key reading for academics and policy makers in physical activity, international exercise, wellness and rehabilitation, and related disciplines, as well as research-focused clinicians in settings where patients with advanced illness are frequently encountered.