Systemic lupus erythematosus is a complex, multifactorial, autoimmune disease. Genetic factors are believed to contribute to its pathogenesis. There have been numerous recent advances in the study of both murine and human lupus genetics. In murine lupus, congenic strains of three susceptibility loci have been developed. Transgenic and knock-out mice models of candidate genes now exist. In association studies of human lupus, the contributions of the MHC loci, Fcgamma receptors, various cytokines, components of the complement cascade, and proteins involved in apoptosis have been explored. Most recently, linkage analyses have been performed and provide numerous regions for further exploration for susceptibility genes. Studies to identify the genes in the susceptibility regions are underway. An understanding of the genes involved in the development of lupus should provide targets for more focused therapy.