Systemic lupus erythematosus is a polycongenic autoimmune disease characterized by the production of antinuclear antibodies that lead to subsequent end organ damage. The study of lupus is complicated by its polycongenic origin, contributions from hormones and the environment, epistasis among susceptibility loci, suppressive modifiers, and the fact that a single susceptibility locus may encompass multiple susceptibility genes. Murine models that develop lupus spontaneously have greatly contributed to our understanding of this disease. In particular, the advent of ?congenic strains' has greatly simplified the study of this complex autoimmune disease. Thus, congenic strains bearing NZB/NZW/NZM2410, BXSB, and MRL lupus susceptibility loci are steadily replacing the traditionally studied murine lupus models as the models of choice for research. This review summarizes how researchers have used congenic strains over the past few years to dissect out and reconstruct the individual elements contributing to lupus pathogenesis.