The endothelium participates actively in homeostatic mechanisms such as the regulation of vascular tone and maintenance of a nonthrombotic environment, as well as directing biological responses such as leukocyte trafficking to inflammatory sites. Disruption of these processes leads to disease. In the antiphospholipid antibody syndrome autoantibodies provoke the endothelium to develop a prothrombotic surface. In systemic vasculitides associated with presence of antineutrophil cytoplasm antibodies, it is likely that the autoantibodies incite premature neutrophil activation, disrupted neutrophil-endothelium interactions and endothelial damage. This review considers how normal endothelial functions may be subverted in disease and how active endothelial responses may contribute to disease.