Desire to restore the balance of body elements has enamored physicians since the ancient practice of bloodletting. More recently, extracorporeal techniques have been employed in both adults and children in treating sepsis. Extracorporeal therapies include continuous renal replacement (CRRT), plasma-based removal techniques, and extracorporeal membrane oxygenation (ECMO). These treatments could theoretically 1) provide immunohomeostasis of pro- and anti-inflammatory cytokines and other sepsis mediators, 2) decrease organ microthrombosis through removal of pro-coagulant factors and modulating the impaired septic coagulation response in sepsis, and 3) provide mechanical support of organ perfusion during the acute septic episode to allow time for response to traditional sepsis therapies and antimicrobials. CRRT is beneficial in managing fluid overload and acute renal failure in sepsis. Removal of sepsis mediators through the technique is variable, and the outcome impact of CRRT on sepsis has not been definitively determined. High-flow CRRT has demonstrated benefit in septic adults. Intriguing early results suggest that plasma exchange could improve outcomes in both adults and children. Based on experience, ECMO is recommended for refractory septic shock in neonates and should be considered for use in children. Ongoing trials may help determine whether the promise of extracorporeal therapies translates into outcome improvement in septic children.