Major advances in understanding the genetic foundation of systemic lupus erythematosus are in the offing. Genetic association studies suggest multiple effects that include those encoded by the HLA region, the genes for Fcgamma receptors and other genes such as that for the mannose-binding protein. Genome scan studies suggest many (at least twelve) genetic linkages with lupus. Identifying the genes linked with lupus is likely to require many years of concerted effort, as well as the availability and evaluation of much larger pedigree collections.