The pathophysiology of sepsis is becoming a more complicated scenario. In sepsis, endotoxin or other gram-positive derived products induce a complex and dynamic cellular response giving rise to several mediators known to be relevant in the pathogenesis of septic shock, such as specific mediators. substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of nuclear factor-kappaB or signal transduction pathways, and precursor molecules. In this article, we delve into some new concepts stemming from the use of sorbents in continuous plasma filtration. The rationale is based on the assumption that the nonspecific removal of several mediators of the inflammatory cascade and cytokine network may improve outcome in a rabbit model of septic shock and hemodynamics in a pilot clinical study. The importance of looking for innovative treatments specifically targeted for the special needs of the critically ill patients rather than using concepts and technology applied to the treatment of chronic renal failure is underlined.