The disorders known as epidermolysis bullosa constitute a group of genetic diseases of the skin which in the mildest form are debilitating throughout life and in the most severe forms result in death at an early age. The profound morbidity associated with all forms of the disease results not only in the loss of an economically productive life but also, in many cases, in the need for continuing medical care throughout life. Inroads are being made into potential pathogenic mechanisms in certain forms of EB. The current state of knowledge can best be characterized as a number of potentially significant disparate observations from various disciplines. The ultimate goals of research in EB are not only to understand the disease but also to provide the biochemical tools for reliable genetic classification, for antenatal diagnosis, and for rational modes of therapy.