FcγRIIs are the most widely distributed of the Fcγ receptor family and play an important role in the clearance of immune complexes. Evidence that the FcγRIIa–R131 allotype is less able to process and clear immune complexes effectively suggests that this may be a disease susceptibility factor for systemic lupus erythematosus (SLE). Data from studies published thus far do not agree on the potential role of FcγRIIa polymorphism in the genetics of SLE. Most studies in fact show no evidence for any correlation between polymorphism of FcγRIIa and risk for SLE. However, it remains to be determined whether FcγRIIa polymorphism may play a critical role in certain groups of patients, especially in those of differing ethnic background. Polymorphism of FcγRIIa may also be important in determining disease phenotype, and identification of this influence may have important implications in patient care and in identifying patients for more aggressive therapy.