In this overview, we describe the advantages, disadvantages, and specific skin and hair abnormalities in spontaneous mouse mutations, as well as sources of information about models generally applicable to skin diseases. These inbred mouse mutations are used directly to evaluate the genetic bases of mammalian skin diseases and indirectly to study the effects of grafting human tissues onto congenitally immunodeficient mice. Such inbred immuno-deficient mice are productively used to study neoplasia and autoimmune diseases; to produce gene products in transfected human cells and to reconstitute the mouse immune system with human cells. The advantages of using inbred mouse mutants dramatically changed when the ability to produce transgenic mice with induced mutations that increase, nullify, or alter the expression of specific genes was created. Combining the best features of spontaneous and induced mouse mutations provides powerful tools to analyze the developmental biology and the diseases of mammalian skin and hair.