Endotoxin is one of the principal biological substances that cause gram-negative septic shock. Lack of clinical success with antiendotoxin or anticytokine therapy has shifted interest to extracorporeal therapies to reduce circulating levels of the mediators of sepsis. Direct hemoperfusion with polymyxin-B-immobilized fiber (PMX-F) is a promising treatment of gram-negative sepsis in critically ill patients. Because of the high affinity of polymyxin B for endotoxin, the rationale underlying extracorporeal therapy would be to remove circulating endotoxin by adsorption, thus preventing progression of the biological cascade of sepsis. In a systematic review of 28 studies (pooled sample size 1,390 patients), the preliminary results of which are described here, PMX-F therapy appeared to significantly lower endotoxin levels, improve blood pressure, and reduce mortality. However, publication bias and lack of blinding need to be considered. These encouraging results need to be verified with large-scale controlled clinical trials.