Fc receptors represent a distinct group of hematopoeitic cell surface glycoproteins that have a characterized role in affecting the efficiency of the mononuclear phagocyte system to clear IgG immune complexes. Functional genetic variations in this family of receptors have been identified as heritable susceptibility factors for SLE and lupus nephritis across diverse populations. In this review, we describe the roles of the classical Fc receptors for IgG (Fc gamma) and non-classical Fc-like receptors (FCR1-FCRL6L), Fc receptors for IgE (Fc epsilon RI) and IgA and IgM (Fc alpha/mu R) in SLE diathesis. The combined effects of these genes on SLE pathogenesis, either via linkage disequilibrium or epistasis with additional genetic or environmental factors, provide a challenge for future investigations. The pursuit of a polygenic SLE-profile that includes longitudinal evaluations of SLE and markers involved in the protean clinical manifestations associated with SLE will facilitate our understanding of the cascade of inflammatory events associated with the diathesis.