Multiple systems organ failure (MSOF) is a relatively new clinical syndrome that should be considered as a unified and identifiable clinical condition. In many ways it is a product of the technologic advances developed in the last few years to treat seriously ill patients. Failing respiratory, renal, and cardiovascular systems are the most frequently encountered combinations, with sepsis, faulty nutrition, and metabolic derangements often present. However, other systems of organs that support vital functions (eg, gastrointestinal, hepatic, neurologic, and coagulation) become additional important components of the MSOF syndrome. The etiology of this entity is multifactorial and difficult to clearly determine. The patients at risk are usually in an intensive care unit and are easy to identify. Because there is no specific treatment, prevention is of utmost importance. When MSOF occurs, correction of the obvious deficits, active support of the failing systems, and prevention of failure of other still functioning systems are the key to survival.