Gram-negative bacterial sepsis and septic shock remain significant causes of morbidity and mortality in hospitalized patients. Recent investigation in this area has served to better define the host response to these and other types of infection, a constellation of signs and symptoms that has been termed sepsis syndrome. Recent studies indicate that the mortality associated with this latter disease process is approximately 40%, despite administration of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. For this reason, the pathophysiology of this process is undergoing intensive examination, and attempts are being made to employ several new types of treatment modalities as adjunctive therapy. Although the initial antiendotoxin antibody trials have not demonstrated the efficacy of these reagents, these studies have provided extremely valuable information regarding appropriate trial design, the current epidemiology of sepsis syndrome (particularly in relation to the ensuing morbidity and mortality), and the pathophysiology of the host septic response and have highlighted the need for rapid, precise diagnostic assays. A number of other intriguing reagents, including anti-TNF-alpha antibody preparations, IL-1ra, bacterial permeability-increasing protein, TNF-binding protein, polymyxin B hemoperfusion, and lipid A analogues also are undergoing experimental and clinical testing in an attempt to reduce the mortality of this lethal disease process.