Gene therapy of hair follicles has has potential for treating disorders of the hair and skin, however, achieving high levels of gene expression remains a serious obstacle to therapeutic applications. In this issue, Cotsarelis and colleagues (p. 420) describe a new method that strikingly increases transfection efficiency of hair follicle cells. They grafted skin from a human scalp onto mice to create a model that faithfully recapitulates the characteristics of human follicle structure and hair cycle, and used this system to test the feasibility of topical liposomes for delivering DNA to the hair follicles. By monitoring the expression of β-galactosidase, they defined the parameters important for transfection, such as liposome composition, timing of application, and pre-treatment with depilation and retinoic acid. They found that their method targets hair progenitor cells, and so has the potential to affect the characteristics of the hair follicle should provide a valuable tool in the testing of genes for treatment of hair and skin disorders.