Summary: A number of features contributed to establishing the mouse as the favorite model organism for skin research: the genetic and pathophysiological similarities to humans, the small size and relatively short reproductive period, meaning low maintenance costs, and the availability of sophisticated tools for manipulating the genome, gametes, and embryos. While initial studies depended on strains displaying skin abnormalities due to spontaneous genetic mutations, the availability of the transgenic and knockout technologies and their astonishing perfection during the last decades allowed the development of mouse lines permitting any imaginable genetic modification including gene inactivation, substitution, modification, or overexpression. While these technologies have already contributed to the functional analysis of several genes and processes related to skin research, continued progress requires understanding, awareness, and access to these mouse resources. This review will identify the strategies currently employed for the genetic manipulation of mice in skin research, and outline current resources and their limitations. genesis 50:652-664, 2012. V V C 2012 Wiley Periodicals, Inc.