The introduction of biologic therapies, which selectively target components of the immune system, has revolutionized the treatment of rheumatoid arthritis. Anti-TNF-alpha therapy (infliximab, etanercept and adalimumab) and B-cell-depleting agents, such as rituximab, are the most widely used agents. Increased experience of the use of biologic drugs in other immune-mediated inflammatory diseases has led to the application of biologic therapies in the treatment of primary systemic vasculitis. Conversely, the success of biological agents has improved understanding of the immunopathogenesis of vascular inflammation. The need for biologic agents arises from the failure of the current standard of care to maintain remission while limiting drug toxicity. Evidence for the efficacy of biologic agents does not match that of conventional immunosuppressants yet, but it is building rapidly. This paper reviews the current evidence for the standard of care of patients with vasculitis and the role of biologic therapy in primary systemic vasculitis. In this review, we examine the rationale for using biologics based on the pathophysiology of primary systemic vasculitis. The risks and benefits of the use of biologics are discussed, together with future directions and predictions of these emerging therapies.