Antibodies produced in response to a foreign antigen are characterized by polyclonality, not only in the diverse epitopes to which their variable domains bind, but also with respect to the various effector molecules to which their constant regions engage. Thus, the antibody’s Fc domain mediates diverse effector activities by engaging two distinct classes of Fc-receptors (Type-I and Type-II FcRs) based on the two dominant conformational states that the Fc domain may adopt. These conformational states are regulated by the amino acid differences among antibody subclasses and by the complex, biantennary Fc-associated N-linked glycan. The diverse downstream pro-inflammatory, anti-inflammatory, and immunomodulatory consequences of Type-I and Type-II FcR engagement are discussed in the context of infectious, autoimmune, and neoplastic disorders.