Recent advances in the molecular biology of the dermo-epidermal basement membrane zone have contributed greatly to our understanding of the etiopathogenetic pathways underlying mechanobullous disorders. Genetic linkage was established between the keratin gene clusters and epidermolysis bullosa simplex, and keratin mutations were identified in several patients. Anchoring filaments and the alpha 6 beta 4 integrin are likely to be affected in junctional EB. Genetic linkage was established between the collagen VII gene and both dominant and recessive subtypes of dystrophic epidermolysis bullosa, and different molecular abnormalities of collagen VII leading to formation of non-functional, rudimentary anchoring fibrils were observed in several families. These discoveries that led to definition of mutations underlying EB also help us to understand the normal physiology and function of the affected structures. They may also point the way to new therapeutic strategies for common acquired blistering diseases and disturbances of epithelialization in general.