The skin barrier function is totally disturbed in atopic dermatitis (AD). Regarding permeability barrier dysfunction, a significant incidence of genetic abnormality in filaggrin in patients with AD is one of the pivotal discoveries, which is stimulating studies on aspects of barrier dysfunction in AD. Currently, permeability barrier homeostasis is one of the most important issues, not only in cutaneous biology, but also in allergology and immunology. Permeability barrier abrogation not only induces cutaneous inflammation, but is also involved in the induction of Th2 type immunological reactions. Conversely, Th2 or other cytokines abrogate permeability barrier homeostasis. In addition to these "Outside to Inside" and "Inside to Outside" relationships between permeability barrier abrogation and allergic inflammation, a new concept called "Intrinsic" cross talk, is proposed in this review. In the "Intrinsic" cross talk" alteration of one macromolecule in keratinocytes affects permeability barrier homeostasis and, simultaneously, induces or augments inflammation.