Receptors for the Fc domain of immunoglobulin G (FcγR) provide an interface between specific humoral immunity and the cellular branch of the immune system through their interaction with antibody. Gross‐linking FcγR on myeloid cells triggers such diverse functions as clearance of immune complexes, phagocytosis of opsonized pathogens, secretion of reactive oxygen intermediates, and antibody‐dependent cellular cytotoxicity. The FcγR play a major role in the removal of antibody‐coated infectious agents and are the exclusive trigger molecules for tumor cell killing by human myeloid cells. Studies of FcγR function have been aided by the use of FcγR specific monoclonal antibodies, self‐directed target cells, and bispecific antibodies that link target cells or pathogens to specific host cell molecules, including FcγR. These reagents have contributed significantly to our understanding of the role of the different classes of FcγR in mediating protection from various infectious agents and in mediating tumor cell killing. Taken together, these approaches have provided insight into the utility of manipulating Fc?R function in the therapy of cancer and infectious disease. J. Leukoc. Biol. 55: 816–826; 1994.