For more than 100 years, clinicians have explored the use of antibody therapy for the treatment of infectious illnesses. The initial use of antibody-based therapies consisted of serum infusions to treat certain infections. The recent developments in hybridoma and recombinant technologies have refined this use with the development of monoclonal antibodies. Monoclonal antibodies that are highly specific and can be directed toward specific pathogens, inflammatory mediators, or tissues receptors have been generated. These characteristics have made them attractive molecules for use in altering the pathogenesis of infectious syndromes leading to the development of septic shock. Experimental models of sepsis and septic shock have been used to demonstrate that monoclonal antibodies directed at specific pathogens or mediators of the proinflammatory cascade can alter or block pathways leading to irreversible shock. This development has prompted clinical trials using monoclonal antibodies aimed at improving the morbidity and mortality of patients with sepsis and the septic shock syndrome. Although clinical trials have yet to clearly define an exact therapeutic role for the use of monoclonal antibodies in altering the pathogenesis of septic shock, they remain intriguing molecules for potential preventive or adjunct therapy for sepsis. We discuss the historical, current, and future prospects of monoclonal antibody therapy in the treatment of sepsis syndromes. Copyright © 2001 by W.B. Saunders Company