Endotoxin, one of the principal components on the outer membrane of Gram-negative bacteria, is considered a key and early component in the pathogenesis of sepsis. Polymyxin B bound to polystyrene fibers (PMX) is a medical device capable of removing circulating endotoxin by adsorption. The most comprehensive analysis to date of clinical experience with this device remains a meta-analysis of 28 studies between 1998 and 2006. This showed that PMX hemoperfusion was associated with improved blood pressure and a reduction in dopamine dose, improved PaO2/FiO2 ratio and lower mortality. Since this meta-analysis, over 50 additional studies on PMX have been published. The majority are observational, with small sample sizes. Notable among the newer studies is the increasing interest in the use of PMX therapy in interstitial pneumonias and idiopathic pulmonary fibrosis, as well as in longer treatment duration and earlier initiation of PMX therapy in an attempt to further improve clinical outcomes. These observational data highlight important aspects of PMX therapy worthy of more rigorous investigation in future studies.