Blocking the effects of cytokines is a potential new therapeutic avenue for the treatment of Gram-negative sepsis. Three classes of agents are currently being evaluated: antibodies, circulating inhibitors, and receptor antagonists. Data in the current literature support the consideration of these agents as potential therapeutic agents in Gram-negative sepsis. The clinical utility of these agents is contingent on the results of well- designed, prospective, randomized, placebo-controlled clinical trials in well-defined clinical populations. These trials will require the cooperation of clinical and basic scientists. At this time, preliminary and early clinical trials are in progress utilizing IL-1 and TNF-α circulating inhibitors, IL-1 receptor antagonists, and monoclonal antibodies to TNF-α and the TNF-α receptor.