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As intensive care moves into its second half century, we are increasingly aware that severe global weakness is a significant debility after a prolonged intensive care unit (ICU) stay, impacting significantly on the pace and degree of recovery and return to former functional status. ICU-acquired weakness (ICUAW) is a common complication of critical illness, particularly in patients receiving mechanical ventilation and/or suffering from conditions leading to the systemic inflammatory response syndrome. The weakness and disability that result from these neuromuscular disorders can dominate the long-term course and impede recovery. Despite the apparent importance of this problem, much remains to be understood about its prevalence, causes, prevention, and treatment.The Brussels Round Table Conference held in March 2009 was dedicated to the topic of ICUAW. The deliberations of the clinicians, physician-scientists, and basic investigators who convened to explore our understanding of this phenomenon are presented in the papers in this supplement. More than 20 experts in the fields of intensive care, neurology, and muscle physiology review current understandings of ICUAW, in the hopes of stimulating and identifying areas for future research.The meeting was organized by Jean-Louis Vincent, MD, PhD, FCCM, Brussels, Belgium. We were honored to act as co-chairs. Meeting participants represented an international body of knowledge: Elie Azoulay, Paris, France; Polly Bailey, Salt Lake City, UT; Laurent Brochard, Creteil, France; Roy Brower, Baltimore, MD; Leigh Ann Callahan, Lexington, KY; Bernard De Jonghe, Poissy, France; Matthias Eickermann, Boston, MA; Greet Hermans, Leuven, Belgium; Margaret Herridge, Toronto, ON, Canada; Malcolm Jackson, Liverpool, UK; John Kress, Chicago, IL; Nicola Latronico, Brescia, Italy; Dale Needham, Baltimore, MD; Scott Powers, Gainesville, FL; Michael Reid, Lexington, KY; Darlene Reid, Vancouver, BC, Canada; Michael Rennie, Derby, UK; Tarek Sharshar, Garches, France; Robert Stevens, Baltimore, MD; and Paul Wischmeyer, Denver, CO.The papers here range from discussions on diagnosis and nosology, risk factors, and pathophysiology to prevention and treatment. The challenges of formal patient evaluation and routine bedside assessment of neuromuscular function are often confounded by complicating factors, such as sedative and analgesic administration. Risk factors for development of ICUAW include bed rest itself, sepsis, and corticosteroid exposure. A strong association exists between weakness and long-term ventilatory dependence. Weakness as a component of global neurocognitive dysfunction is a major determinant of patient outcomes after acute respiratory failure and may be present for months or indefinitely in the convalescence phase of critical illness. Much has been learned about the physiology and cell and molecular biology of skeletal and diaphragm dysfunction under conditions of aging, exercise, disuse, and sepsis, but the application of this knowledge to the bedside requires more study in both bench models and patients. Although a trend toward greater immobilization and sedation of patients has characterized the past several decades of ICU care, recent studies have demonstrated that early physical and occupational therapy—including during the period of intubation and ventilatory support—can be performed safely and likely improve patient outcomes with regard to functional status.We thank Jean-Louis Vincent for the insight in bringing together this Round Table as well as the participants who contributed so generously their time and efforts to make this endeavor a success. We hope the readers likewise will be stimulated and enthused by the papers presented in this supplement. We believe they make a substantial contribution to improving the well-being of our patients.