Sepsis is still associated with a high mortality rate. Septic shock and sequential multiple organ failure have a strong correlation with poor outcome. Lipopolysaccharide (LPS) plays a pivotal role in the initiation of host responses to Gram-negative infection. A number of mediators, such as cytokines, nitric oxide and eicosanoids, are responsible for most of the manifestations caused by LPS, and circulatory failure, leukocyte-induced tissue injury and coagulation disorder appear to be critical determinants in the development of sequential organ failure. Although several anti-LPS or anti-cytokine clinical trials have been attempted, none of them has so far been successful.