Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides are rare autoimmune diseases that can often be life threatening. They particularly affect the kidneys and lungs but can also affect many other organs. Various hypotheses have been proposed to explain the loss of tolerance against ANCA antigens (present in granules of neutrophils and monocytes); however, clear mechanisms remain elusive. Clinical observation, in vitro studies and newly developed animal models implicate ANCAs in disease pathogenesis and relevant mechanisms are now being characterized. Abnormalities in patient's T-cell populations exist and the increasingly recognized role of B cells in ANCA-associated vasculitis is also discussed.