Desmosomes guarantee the integrity of the epidermis, by functioning both as an adhesive complex and as a cell-surface attachment site for the keratin intermediate filaments of the cytoskeleton. Considerable progress has been made in our knowledge of desmosomes and their components. The structure and function of many of the desmosomal molecules have been determined, and a number of the molecular interactions between desmosomal proteins have been elucidated. Desmosomal proteins are major antigens in pemphigus. Each type of pemphigus has its own antigenic targets, but in the last few years it has been shown that certain autoantibody populations are not restricted to just one form of pemphigus. The production of autoantibodies against multiple intracellular and extracellular desmosomal proteins, whose pathogenic role remains to be elucidated, suggests an overlapping distribution of antibody specificities among different forms of pemphigus.