Antiendothelial cell antibodies represent a heterogeneous group of antibodies directed against a variety of antigen determinants of endothelial cells. Antibodies reacting with endothelial structures have been detected in sera from patients with autoimmune vasculitis, both primary and secondary to systemic connective tissue diseases. It may interfere with several functions and, therefore, may be a pathophysiological relevance. The analysis of the antigens recognized by antiendothelial cell antibodies showed that the antibodies are directed against a heterogeneous family of both constitutive and nonconstitutive surface endothelial proteins. Proteomics is a field of science that evaluates a large number of proteins expressed from a given cell line or organism. The technology of proteomics has been used as a method for discovering the target protein specific to a particular disease by searching for the expression or modification of the protein. Recently, progress has been made in defining the target antigens of these antibodies and proteomic technologies is one of them. This review will focus on the proteomic technologies in searching autoantigens/autoantibodies associated with disease of the endothelium.