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Sepsis represents a lethal dysregulated host response to infection leading to organ dysfunction. Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, preventing multiorgan failure. Even in the absence of strong indications deriving from large clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Different therapies have been developed to address certain steps of the immune dysregulation besides classical renal replacement therapy, such us High Volume Hemofiltration, High-cut-off membrane hemofiltration, hemoadsorption treatments and coupled plasma filtration and adsorption. Despite the different underlying mechanisms of action, most of such available devices focus on a single target, such as endotoxins, cytokines, or both, that triggers the inflammatory cascade. The attention in this review is focused on presenting Blood Purification Techniques and the evidence of their clinical effectiveness, clarifying the indications, ideal patient selection, timing, dosing and biomonitoring, important issues that should be solved in the future, to enable usage of these therapies in the best possible and most targeted manner.