Postinjury multiple organ failure (MOF) became prevalent as the improvements in critical care during the 1970s made it possible to keep trauma patients alive with single organ injury. Enormous efforts invested in laboratory and clinical research made it possible to better understand the epidemiology and pathophysiology of the syndrome. This has translated to improved strategies in prediction, prevention and treatment of MOF. With changes in population demographics and injury mechanisms and improvements in trauma care, changes in the epidemiology of MOF are also becoming evident. Significant improvements in trauma patient management decreased the severity and mortality of MOF, but the syndrome still remains the most significant contributor of late postinjury mortality and intensive care unit resource utilisation. This review defines the essential MOF-related terminology, summarises the changing epidemiology of MOF, describes our current understanding of the pathophysiology, discusses the available strategies for prevention/treatment based on the identified independent predictors and provides future directions for research.