The primary small vessel systemic vasculitides are disorders that target small blood vessels, inducing vessel wall inflammation and associated with development of antineutrophil cytoplasmic antibodies. Multiple organs are attacked including the lungs and kidneys. Increasing knowledge of pathogenesis suggests that the antibodies activate neutrophils inappropriately, leading to endothelial and vascular damage. Cytokines such as tumour necrosis factor (TNF) can facilitate the damage by priming neutrophils and activating endothelial cells. Understanding pathogenesis can help to rationalise existing therapies and indicate new approaches to therapy such as the use of agents that inhibit the effects of TNF.