Anti-TNFalpha blockers are extensively used in the management of chronic inflammatory disorders. Their administration may be associated with the generation of autoantibodies; this review focuses on the autoimmune phenomena linked to anti-TNFalpha inhibition, on the hypothesized pathogenetic mechanisms and on the clinical implications. While the development of antinuclear and, less frequently, of anti-DNA antibodies is a common finding, the onset of autoimmune diseases during anti-TNFalpha blocker treatment is a rare event, which needs to be promptly recognized in order to plan the appropriate management. Moreover the specific autoantibodies associated with rheumatoid arthritis are considered before and after biotherapy. Similarities and differences among infliximab, etanercept and adalimumab concerning induced autoimmune phenomena are underlined.