Although the pathogenesis of systemic lupus erythematosus (SLE) might now seem very complicated, various aspects are coming together to make a coherent story. Firstly, there is a loss of tolerance by the T and B lymphocytes, so accounting for the formation of autoantibodies that characterize this autoimmune disease. Failure of methylation of vital genes could underlie this aspect. Secondly, as much emphasized in recent years, poor clearance of apoptotic cells on account of de-fective phagocyte receptors and complement deficiencies involves stimulation of Toll like Receptors (TLRs) 7 and 9 on plasmacytoid dendritic cells (pDCs) and results in release of type I interferon alpha (IFNa). Thirdly, the familiar Th-1 lymphocytes produce interleukins 12 and 18 and inter-feron gamma (IFNy)), along with chemokines, but now Th-17 lymphocytes are recognized to play an important role.