A key function of the skin is to provide a permeability barrier to restrict the movement of water, electrolytes, and other small molecules between the outside environment and the internal milieu. Following disruption of the permeability barrier, there is a rapid restoration of barrier function, and one of the key signals initiating this repair response is a decrease in the concentration of calcium in the outer epidermis. In this issue, Borkowski et al. present evidence showing that activation of Toll receptor 3 by double-stranded RNA may be another pathway for activation of permeability barrier repair. These results provide further evidence for a link between innate immunity and the permeability barrier.