A variety of rheumatic disorders have been successfully treated with tumour necrosis factor (TNF) blockers. However, TNF blockade may be useful in a number of rare diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists-Behcet's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis have been shown to improve with infliximab but not with etanercept. These results lend further support for the concept of differential mechanism(s) of action of the two antagonists with infliximab being more effective for the treatment of granulomatous diseases. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjogren's syndrome as evidenced by the lack of efficacy of both TNF antagonists. Etanercept has been shown to be useful in the treatment of hepatitis C both in reducing the viral load and improving liver function. A number of other more rare disorders also may be responsive to TNF blockade. Further studies with larger numbers of well characterised patients and treatment regimens are necessary to provide more definitive evidence of the utility of the TNF antagonists in these serious and often life threatening diseases.