The candidate gene approach in tracking the underlying cause of a number of genetic skin disorders has proved remarkably effective over the past few years. Electron microscopy has had a unique role in identifying morphologic abnormalities of various fibers, fibrils, and filaments, and helping to localize biochemical constituents to these structures. Nowhere is this approach more strongly demonstrated than in its application to different forms of epidermolysis bullosa, of which two major forms, junctional and dystrophic epidermolysis bullosa, are caused by mutations of genes encoding structural proteins in the dermal-epidermal junction.