The past two years have brought great progress in the genetics of systemic lupus erythematosus (SLE) heralded by the publication of genome-wide association studies in humans and the identification of susceptibility genes in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. SLE is a complex disease in which defects in several functional pathways have been identified. Genetic variants in a number of genes in these pathways have now been directly associated with lupus in both species. These discoveries have lead to a better understanding of the mechanisms of disease, and offer potential novel target for therapeutic intervention. As a large number of susceptibility genes are identified, lupus genetics will focus on mechanistic and molecular studies, in which mouse models will continue to serve a pre-eminent role.