Systemic lupus erythematosus (SLE) is a systemic non-organ specific autoimmune disease associated with multiple autoantibodies targeting autoantigens from the nucleus. Given the complex pathophysiology of SLE and the role of TNF alpha in that disease, modulation of TNF alpha (in SLE or non-SLE patients) using TNF blockers could either be detrimental or beneficial in some patients. In this review we will focus on lupus autoantibodies and clinical manifestations after TNF blockade in SLE patients and conversely on drug-induced-SLE in non-SLE patients. Some hypotheses regarding the mechanism of induction of autoantibodies in RA patients treated with TNF blockers are proposed.