Small-vessel vasculitis is defined by the presence of blood vessel inflammation involving the arterioles, venules, or capillaries. This can be seen in a broad spectrum of settings, but it is most commonly associated with Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Although prednisone combined with cyclophosphamide induces remission and prolongs survival in these diseases, this regimen is toxic and does not prevent relapse. Current therapeutic approaches seek to minimize cyclophosphamide exposure through the use of staged induction-maintenance regimens or cyclophosphamide alternatives for induction of nonsevere disease. Emerging trials with biologic agents are exploring new treatment options.