The appearance of biologic agents for the treatment of diverse autoimmune diseases in particular rheumatoid arthritis at the end of the 1990s changed the treatment of these patients. With the introduction of new agents in the treatment of rheumatic diseases, we started to notice the presence of new and sometimes unexpected adverse events. It is well recognized that infections are the main concern with these types of treatments; however, the occurrence of autoimmune abnormalities is also seen and its gaining perhaps more attention as the use of these agents is increasing. The first clinical trials of anti-tumor necrosis factor-α (anti-TNFα) inhibitors showed an increase of antinuclear and anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies in patients treated with these agents. In this paper, we review the frequency of these autoantibodies in patients treated with biologic agents, particularly anti-TNF-α inhibitors, and its correlation with autoimmune processes as well as the clinical relevance of such findings.