We searched for innovative treatments specifically targeted to the cytokines of three critically ill patients with streptococcal toxic shock syndrome (STSS). Direct hemoperfusion with polymyxin B-immobilized fiber improved the hemodynamics in all three patients who had developed shock at presentation. Continuous hemodiafiltration coupled with plasma exchange for simultaneous removal of several mediators of the inflammatory cascade improved outcome in case 2 and lessened the aggressive clinical course and prolonged survival in case 3. The application of these technologies appears to open new and interesting therapeutic options and may lead to improved survival in STSS.