In this review, we focus on current information on the apheresis procedures for endotoxins removal with Polymyxin B cartridges (PMX). This device has been designed in 2003 in Japan in order to take advantage of the antibiotic effects of Polymyxins on Gram negative bacteria and endotoxins, by-passing the toxicity shown by the intravenous administration. Although its mechanisms of action are nowadays well-known, we felt the need to sum up all the someway scattered information giving an overall sight on the entire process that brings Polymyxins molecules to function as powerful detergents of the endotoxins from the blood flow. Since the first experiences on humans, over one hundred studies have been published about the clinical use of this device. Even if some of them were limited in number of patients and compliance to international standards, they all converged in showing a highly positive impact of PMX on the improvement of clinic condition and outcome. Recently, more significant and large experiences confirmed the benefits of this treatment on hemodynamic, PaO2/FiO2 ratio, APACHE and SOFA scores and outcome at 28 days even on different typologies of sepsis cases, such as in transplanted patients. Summarizing, this relatively new procedure has proven to be a promising tool against Gram negative and endotoxin sepsis, combining clinical and outcome improvements with a fair cost/effectiveness ratio. Given that, there’s still need of wider and more structured clinical studies that could steady the use of this device and widen its fields of applications.