The expanding range of biologic agents capable of modulating the immune response has opened up a new realm for therapeutic exploration in the vasculitic diseases. Partnered with increasing knowledge regarding the mechanisms of vascular inflammation, these agents have raised the question as to whether it may be possible to treat systemic vasculitis syndromes by selectively targeting pathways involved in disease pathogenesis. The action of these agents to directly modulate specific immunologic components offers the potential not only to impact disease activity but also to reduce the risk of morbidity that can result from currently available treatment options. The study of biologic therapies in the vasculitides must, however, be approached with caution because unanticipated effects on disease activity and disease-specific toxicities can occur. The only biologic agent that has currently been shown to have therapeutic efficacy in a systemic vasculitis syndrome is interferon-alpha in the treatment of hepatitis C-associated cryoglobulinemic vasculitis. The use of biologic agents to treat other vasculitides remains investigational. Methodical evaluation of biologic agents prior to their use in general clinical practice is essential to understand their safety and efficacy. Rigorous, standardized investigations may also provide important insights into pathogenesis of the vasculitic diseases.