Lupus nephritis (LN) is a prototypic autoimmune disease. Its immunopathogenesis is characterized by the loss of self-tolerance. In this article, we review our current understanding of the disease mediators of LN. There is ample evidence to suggest a pathogenic role of nephritogenic autoantibodies. These antibodies cross react with nucleosomal epitopes, and the in vivo generation of nucleosomes requires apoptosis. Furthermore, there is an intriguing and paradoxical relationship between complement and systemic lupus erythematosus (SLE). Immune complex-mediated activation of complement through the classic pathway is traditionally believed to be a major mechanism by which tissue injury occurs. In contrast, hereditary deficiencies of complement components increase the risk of SLE. Finally, the roles of reactive nitrogen and oxygen species are emphasized.