The chronic autoimmune diseases include multiple complex genetic disorders. Recently, genome-wide association studies (GWAS) have identified a large number of major loci, with many associations shared between various autoimmune diseases. These associations highlight key roles for lymphocyte activation and prioritize specific cytokine pathways and mechanisms of host-microbe recognition. Despite success in identifying loci, comprehensive models of disease pathogenesis are currently lacking. Future efforts comparing association patterns between autoimmune diseases may be particularly illustrative. New genomic technologies applied to classic genetic studies involving twins, early onset cases, and phenotypic extremes may provide key insights into developmental and gene-environment interactions in autoimmunity.