The endothelium is the back-drop against which the effects set in train by interactions between Anti-Neutrophil Cytoplasm Antibodies (ANCA) and neutrophils are played out. This review considers the mechanisms of the endothelial cell injury that may result but also questions the impact of endothelial heterogeneity and endothelial cell activation in facilitation of vasculitic lesions, as well as the potential roles for endothelial-dependent anti-inflammatory mechanisms in controlling inflammation.