Endothelial cells play a pivotal role in the pathogenesis of systemic vasculitis. Endothelial cells have significant proinflammatory activities, amplifying and perpetuating the inflammatory process and contributing to vessel regeneration and repair. Significant contributions have improved the understanding of additional ways through which antineutrophil cytoplasmic antibodies (ANCA) may potentiate neutrophil- and monocyte-mediated endothelial cell activation and damage. Signaling pathways mediating ANCA effects have been delineated, and new animal models have demonstrated the pathogenic role of ANCA in the development of systemic vasculitis. Significant efforts have identified anti-endothelial cell antibody specificities and elucidated mechanisms through which these antibodies may promote endothelial cell activation and injury. New ways to assess in vivo endothelial cell damage and dysfunction also have been developed. In addition, besides being a relevant compensatory mechanism for ischemia, angiogenesis may have important proinflammatory functions in vasculitis. The potential relevance of bone-marrow-derived endothelial cell precursors in neovascularization has begun to be appreciated.