Endotoxemia, whether primary (due to Gram-negative infection) or secondary (due to epithelial barrier dysfunction), appears to be extremely common in the critically ill and injured. High levels of endotoxin activity are associated with worse clinical outcomes. In Japan, polymyxin B hemoperfusion has been available to treat endotoxemia for more than ten years. Multiple small trials, often limited by methodological quality, show that polymyxin B hemo-perfusion may have favorable effects on survival and hemodynamics. Further study of this therapy would seem justified.