Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous presentation and clinical manifestations. These aspects represent a problem in the treatment of the disease. Nonspecific medications for SLE that include antimalarials, corticosteroids, and cytotoxic drugs improve the prognosis of SLE yet carry significant side effects. Therefore, new targeted therapies that block pathways involved in the pathogenesis of SLE have been developed as possible additions to the standard management of the disease. This work reviews the current therapies and novel approaches in the treatment of SLE. Drug Dev Res 72:561–572, 2011. ©2011 Wiley Periodicals, Inc.