Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) comprise the most common group of primary systemic vasculitides and include Wegeners granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and renal-limited vasculitis (RLV). AAV share the feature of necrotizing predominantly small vessel vasculitis, but are otherwise distinct diseases with differences in the genetic background, epidemiological and exogenous factors, immune and pathologic features, preferences of organ involvement, and frequencies of ANCAassociation. MPA and RLV display solely vasculitic features, whereas WG and CSS are characterized by both granulomatous disease and a systemic vasculitis. Chronic inflammation and neoformation of tertiary lymphoid tissue appear to initiate and maintain the break of tolerance and induction of ANCA in AAV. A number of mechanisms are implied in this process, e.g., nasal S. aureus carriage suggestive of a potential link to infection in WG, danger-signals, neutrophil extracellular traps (NETs), the protease-activated receptor (PAR)-2, cytokines (Th1/Th2-type, IL-15, IL-17), and NK-like Tcells. The outcome of AAV has greatly improved since the introduction of immunosuppressive therapy. Still, the prognosis is impaired by high relapse rates and side effects of immunosuppressive therapy. Biologicals emerged as a new class of drugs that may help to improve outcome and reduce side effects of conventional treatments. So far, anti-CD20 therapy (rituximab) and TNF-α-antagonists represent strategies for refractory disease, but evidence from controlled trials is still lacking. Controlled trials for “routine” remission induction with these biological are also pending. New therapy principles hold further promise for the future.