In this review, we have attempted to classify the genetically transmitted, generalized disorders of cornification according to available genetic, clinical, and biochemical data (Table 1). Admittedly, the list is long and sure to be lengthened, but this manner of delineation is required to uncover the underlying biochemical causes of the DOC. Grouping diseases according to artificial and outmoded standards clearly impedes this effort, as well as undermines a scholarly approach to patients, because important information about disease expression, differences in inheritance patterns, and subtle, but important, differences in responsiveness to therapy may be obscured by classification of an entity on the basis of overly simplified diagnostic criteria. Thus, clinicians should be wary of classification schemes based solely upon phenotypic similarities, because they may not be based upon valid genetic or biochemical criteria. Clearly, the classification offered in this article must be considered provisional, and it should be modified as new information is acquired. Despite our desire to recognize and codify distinct genetic disorders, this has not been possible in all cases, such as in DOC 17 (chondrodysplasia punctata syndromes), which almost certainly includes more than one genetic entity.