TNF-alpha is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune and non-autoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well-tolerated in patients with Crohn's disease and rheumatoid arthritis (RA) and has become a widely used treatment for these diseases. More recent controlled trials have also shown the effectiveness of TNF-alpha blockers in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The results of clinical trials, open-label studies, and case studies indicate that TNF inhibitors (alone or in combination with other protocols) look very promising for the treatment of a variety of other conditions, including uveitis, sarcoidosis, Sjögren's syndrome (SS), Behcet's syndrome, vasculitis, and graft versus host disease. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. The neutralisation of TNF might therefore play a role in the treatment of many autoimmune and non-autoimmune disorders other than Crohn's disease or RA. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions that do not currently have FDA or EMEA approval.