Current therapies for sepsis are unsatisfactory, with a 50% mortality rate in patients with septic shock, regardless of etiology. Persuasive evidence shows that the majority of damage induced during sepsis is pursuant to induction and overproduction of endogenous cytokine immune mediators. Interleukin-1 and tumor necrosis factor act synergistically as strategic triggers of the cascade of cytokine-induced pathophysiology. Anticytokine therapeutic strategies, directed primarily at interleukin-1 and tumor necrosis factor modulation, have produced preliminary but exciting results in treating sepsis and other inflammatory diseases.