Targeting tumor necrosis factor alpha (TNF-alpha) has offered an additional therapeutic strategy against several rheumatic inflammatory disorders. The current use of TNF-alpha inhibitors allows physicians who manage these diseases and patients themselves to testify to an extraordinary efficacy, even though caution for possible adverse events must be maintained. Among these, the occurrence of autoimmune phenomena, encompassing new autoantibody formation and triggering of clinical manifestations, continues to be noted in published reports. Here, we review the current knowledge regarding the autoimmune phenomena linked to anti-TNF-alpha therapy in patients with rheumatic inflammatory disorders.