Animal models based on knock-out or transgenic technology are widely used in basic and applied biomedical research. An alternative to these approaches is the generation of xenogeneic transplantation models allowing the in-vivo investigation of cell types and organs. In the field of dermatology transplantation of human skin onto mice lacking functional B and T cells (SCID mice) and subsequent manipulation of these grafts yielded new insights in many different aspects of skin biology. This review highlights some of the applications of this versatile model focussing on phenomena relevant for the subject of dermatology.