Systemic lupus erythematosus (SLE) is a systemic autoimmune disease 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. However, recent advances in genetic resources and technology have been providing new tools to identify the novel pathways or the sequence variants that contribute to autoimmune diseases. During the past several years, several new candidate genes have been implicated in development of SLE though association studies. In this article we describe an overview of the latest findings in the genetics of SLE, especially focusing on the genetic variations in the signalling or immunoregulatory molecules including CD28 and IRF family members.