Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. This study was performed as a systematic review to evaluate the efficacy and mechanism of PMX treatment in patients with septic shock. The PubMed database and references from identified articles were used to search and review the literature relating to the efficacy and mechanism of PMX treatment in patients with septic shock. Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes, activated neutrophils, and anandamide, as well as endotoxin through direct covalent bond, hydrophobic and ionic interactions, and hydrodynamics, and reduced the blood concentrations of inflammatory cytokines, plasminogen activator inhibitor 1 and adhesion molecules. Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents. The meta-analysis showed that PMX treatment had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality. These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.