Our knowledge about human Fc gamma receptors has increased dramatically within the last several years. Their structural diversity presents a rich framework within which to understand how immunoglobulins and immunoglobulin complexes activate such a broad range of cell programs relevant to autoimmune diseases. Alleles of Fc gamma receptors provide a new perspective within which to define the interplay between the qualitative and quantitative humoral immune response and host genotype and to identify heritable risk factors for disease susceptibility. With recent insights into the role of Fc gamma receptors in the pathophysiology of inflammatory lesions, we can also anticipate important advances in therapeutic intervention.