Genome wide linkage studies in human SLE have identified seven highly significant loci linked to SLE, and more than 20 other loci showing suggestive linkage to disease. However, pin-pointing the susceptibility alleles in candidate genes within these linkage regions is challenging, due the genetic heterogeneity, racial differences and environmental influences on disease aetiology. Utilization of murine models of spontaneous lupus nephritis provide a complementary approach, which may then identify candidate genes for analysis in human cases. This review highlights the utility of cross-species approach to identify and characterize the effect of given candidate genes in lupus. The examples described in this review demonstrate the importance of bringing together both genetic and functional information in human and mouse studies.