TNFalpha plays a crucial role in the physiopathology of a large number of auto-immune and/or inflammatory systemic diseases. In addition to authorized indications including rheumatoid arthritis, ankylosing spondylitis, Crohn disease, ulcerative colitis, psoriatic arthritis and plaque psoriasis, TNFalpha blockers have been tested in a wide range of auto-immune and/or inflammatory diseases. TNFalpha blockers might be an option in refractory ANCA-associated vasculitis, sarcoïdosis, adult onset Still disease, Behçet disease, AA amyloïdosis and TRAPS. However, pertaining to the limited number of prospective randomized trails available, the small number of patients included and the poor methodology, it is difficult to define their place in the therapeutic strategy in these conditions. The therapeutic effect of TNFalpha blockers is often suspensive and disease flares are frequently observed during sustained treatment, as in the case of Behçet's disease. Published data do not support the use of TNFalpha blockers in connective tissue diseases.