Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex genetic basis that includes many susceptibility genes on multiple chromosomes. As complex human diseases like SLE involve multiple, interacting genetic and environmental determinants, identifying genes for complex traits is challenging and has had limited success so far. Several key approaches that are necessary to identify disease susceptibility genes in common diseases such as SLE are now available. Collectively, these approaches will allow the prioritization of candidate genes based on available knowledge of map position and biologic relevance. They will also allow us to obtain the genomic structure of these genes as well as to study sequence variants that will facilitate the identification of genes that are important in the development and expression (severity) of lupus and associated phenotypes. Although it is still a labor-intensive and expensive project to identify susceptibility genes in common diseases such as SLE, the new techniques that are now being used will undoubtedly improve gene mapping in such a kind of diseases. In this review we highlight the current findings in the genetics of human SLE after using these approaches.