The need for novel approaches to treat infectious diseases is obvious and urgent. This situation has renewed interest in the use of monoclonal antibodies (mAbs) to treat infectious diseases. During the last 5 years, radioimmunotherapy (RIT), a modality developed for cancer treatment, has been successfully adapted for the treatment of experimental fungal (C. neoformans and H. capsulatum), bacterial (S. pneumoniae and B. anthracis), and viral (HIV-1) infections. RIT produced none or only transient hematological toxicity in experimental animals. Investigation of radiobiological mechanisms of RIT of infections showed that microbial cells are killed by both "direct-hit" and "cross-fire" radiation. mAbs radiolabeled with either alpha- or beta-emitters stimulated apoptosis-like cell death, whereas only mAbs radiolabeled with alpha-emitter (213)Bi also decreased the metabolic activity of microbial cells. The success of this approach in laboratory studies, combined with earlier nuclear medicine experience in preclinical and clinical studies using radiolabeled organism-specific antibodies for imaging of infections, provides encouragement for the feasibility of therapeutically targeting microbes with labeled antibodies. We envision that first the organism-specific mAbs will be radiolabeled with imaging radionuclides such as (99m)Tc or (111)In to localize the sites of infection with single-photon emission computed tomography, followed by RIT with (188)Re- or (90)Y-labeled mAb, respectively. Also, immuno-position emission tomogrpahy might be used to image infection before treatment if such positron-emitting radionuclides as (86)Y (matching pair for (90)Y) or (124)I (matching pair for (131)I) are available. It might be possible to create a so-called "pan-antibody" that would recognize an antigen shared by a particular class of human pathogens such as fungi, for example. The availability of such antibodies would eliminate the necessity of having antibodies specific for each particular microorganism and would enormously enhance the development of RIT of infectious diseases.