Vasculitis is histologically defined by the presence of blood vessel inflammation. It can be observed in a wide variety of settings, either occurring secondarily to another process or as the pathologic foundation of a primary vasculitic disease. The primary systemic vasculitides comprise a broad group of disease entities that are uniquely identified by the nature of their clinical, histopathologic, or therapeutic characteristics. Individual diseases often predominantly affect blood vessels of a particular size, the pattern of which influences their clinical manifestations and has been used in their classification. The vasculitides span a wide range of disease severity, extending from illnesses that rarely produce death to those almost universally fatal before the introduction of effective therapy. Immunosuppressive and cytotoxic agents are used to treat many vasculitic diseases. Although such approaches can be effective, long-term treatment may be complicated by chronic sequelae from organ damage, disease relapses, and medication side effects. Recent investigations have focused on understanding the pathophysiology of these diseases, which may lead to more efficacious and less toxic therapeutic options. (J Allergy Clin Immunol 2003;111:S602-12.)