Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of potentially life-threatening disorders characterized by necrotizing small vessel vasculitis with positive serum ANCA. To date, the pathogenesis of AAV has not been fully elucidated, but remarkable progress has been achieved in the past few decades. In this review, we summarize the mechanism of AAV. The pathogenesis of AAV involves various factors. ANCA, neutrophils, and the complement system play key roles in disease initiation and progression, forming a feedback amplification loop leading to vasculitic injury. Neutrophils activated by ANCA undergo respiratory burst and degranulation, as well as releasing neutrophils extracellular traps (NETs), thus causing damage to vascular endothelial cells. Activated neutrophils could further activate the alternative complement pathway, leading to the generation of complement 5a (C5a), which amplifies the inflammatory response by priming neutrophils for ANCA-mediated overactivation. Neutrophils stimulated with C5a and ANCA could also activate the coagulation system, generate thrombin, and subsequently cause platelet activation. These events in turn augment complement alternative pathway activation. Moreover, disturbed B-cell and T-cell immune homeostasis is also involved in disease development. In-depth investigation in pathogenesis of AAV might help to offer more effective targeted therapies.