Immune complexes are major pathogenic factors contributing to tissue injury in a number of autoimmune diseases. Immune complexes consist of autoantibodies to self-antigens, which initiate an inflammatory response through binding to immunoglobulin Fc receptors (FcRs) or via complement components. The significance of FcRs as regulators of inflammatory reactions was defined when mice with genetically engineered deficiencies of FcRs became available, giving new insight into the mechanisms involved in the pathogenesis of immune complex-mediated inflammation and autoimmunity. In this review, some of the most prominent work on inflammation and autoimmunity in animal models, will be presented. This body of knowledge has not only contributed to our understanding of the importance of FcRs in inflammatory autoimmune responses, but more specifically, has paved a new way for designing novel therapeutic compounds in treating autoimmune diseases.