Tumor necrosis factor (TNF) alpha plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept and adalimumab) represents an important tool for the management of a variety of disorders, such as rheumatoid arthritis, the spondyloarthropathies, inflammatory bowel disease and psoriasis. Nonetheless, theoretically, some other autoimmune and inflammatory disorders may benefit from these agents. We intend to update on these off-label uses of anti-TNF blockers in this review.