The concept of multiple organ failure and related abnormalities was first developed in the 1970s. Multiple organ failure became evident when the support systems in intensive care units were able to keep patients alive long enough for multiple organ problems to develop in them. The high mortality of patients with multiple organ failure provided a focus for the problems that ultimately led to death for many patients in the intensive care unit. The frequency of infection, sepsis, or inflammation in producing multiple organ failure led to clinical trials of so-called magic bullets for the treatment of patients with sepsis. These trials have had either limited success or negative results, despite considerable evidence for efficacy or protection by such agents in experimental animals and in studies of normal human volunteers. I believe a major reason for these negative results has been the use of general entry criteria for the trials rather than the treatment of specific diseases or injuries.