The purpose of this review is to highlight recent progress in defining the effects of variation in the germline DNA sequence on the susceptibility to systemic lupus erythematosus.The genetic contributions to lupus susceptibility have been increasingly defined in recent years, although a large proportion of the genetic heritability of this disease remains undiscovered. Various approaches have been taken to determine this 'missing heritability' and to further characterize the known genetic effects in order to more fully elucidate the cause and pathogenesis of this complex and heterogenous disease.Characterizing the genetic contributions to lupus and their functional effects will advance our understanding of the biology of this disease and aid in the development of new therapeutics.