Anti-neutrophil cytoplasmic antibodies (ANCA) are a heterogenous group of autoantibodies with a broad spectrum of clinically associated diseases. ANCA testing has been established as a useful tool for the diagnosis of small vessel vasculitides, especially of 'ANCA-associated vasculitides' (AAV), such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, in which circulating ANCA are commonly found. Within the last 20 years these antibodies were subject of intensive studies and a growing body of evidence arose for a distinct role of ANCA in the pathogenesis of the AAV. Our current concept of whether ANCA directly or indirectly contribute to vascular damage (ANCA-cytokine-sequence-theory) was mainly developed from in vitro studies and is supported by data from clinical investigations as well as animal models. Recently a direct causal link between ANCA and the development of glomerulonephritis and vasculitis has been demonstrated. We now know that a passive transfer of ANCA is sufficient to induce disease, but it remains to be discovered how the autoantibodies to neutrophil antigens might triggered.