System lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that cause widespread tissue damage. The underlying etiology remains largely unknown. Aberrant epigenetics plays essential roles in the pathogenesis of SLE. This review explores the links between DNA methylation, histone modifications, and miRNAs in SLE and highlights how these factors may interact in SLE pathogenesis. We also discuss how furthering our knowledge of epigenetics in lupus provides hope for finding new diagnostic and prognostic biomarkers and novel therapeutic targets and strategies.