The rôle of a genetically-impaired epidermal barrier as the primary cause of the rapid increase in prevalence of atopic dermatitis and respiratory atopy is proposed, based on available clinical and experimental data. The subsequently increased exposure to irritants and allergen postnatally in predisposed individuals would lead in a subset of these to a specific TH2 cell activation favouring the development of IgE responses to atopens. Other routes of sensitization are probably important, but skin offers a good target to implement prevention strategies, so far completely ignored in the prophylactic recommendations given to high-risk families. Candidate genes for skin-barrier impairment are possibly those associated with ichthyosis vulgaris and X-linked hypohidrotic ectodermal dysplasia.