Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCA. Although these autoantibodies were initially used to classify pauci-immune vasculitis, increasing clinical and experimental evidence now supports their pathogenic role, mainly through ANCA-induced activation of primed neutrophils and monocytes leading to destructive vascular necrosis. The mechanisms of ANCA generation remain however unclear. Neutrophils play a central role in the pathophysiological process of AAV since they are both effector cells responsible for endothelial damage and targets of autoimmunity. Another role of neutrophils is due to their ability to generate neutrophil extracellular traps, which support the presentation of ANCA autoantigens, could break immune tolerance and induce autoantibody generation. Alternatively, the ANCA autoimmune response is facilitated by insufficient T-cell and B-cell regulation, and the role of complement alternative pathway has recently been emphasized. This review summarizes the main pathogenesis concepts of AAV as well as the putative mechanisms for the origin of ANCA autoimmune response.