The past, present, and emerging roles of immunotherapy, including the use of monoclonal antibodies for diagnosis and treatment, are discussed. Although immunotherapy has been used for more than 100 years, it became less important when antimicrobial agents came into widespread use. In the 1970s investigators began to re-examine immunotherapy for potential use in gram-negative infections. Polyclonal antiserum against the J5 mutant of Escherichia coli (gram-negative lipid A) has been shown to be effective in treating patients with bacteremia and septic shock. The discovery of monoclonal antibodies and the creation of hybridoma technology by the fusion of immortal cells with antibody-producing cells have resulted in the production of large amounts of monoclonal antibodies of desired specificities. More recently, murine monoclonal antibodies have been used clinically for immunosuppression in renal-transplant patients (OKT3 antibody) and for prevention of septic complications in patients with suspected gram-negative infection and evidence of systemic response (E5 IgM antibody). E5 antibody directed against gram-negative bacterial endotoxin has been reported to significantly reduce morbidity and mortality from gram-negative sepsis and to be well tolerated. The application of new treatment modalities such as monoclonal antibodies is expected to enhance the therapeutic options available to treat infectious diseases.