Despite significant structural differences, the surface epithelia of flies and mice exhibit remarkable functional parallels. Genetic studies in both organisms have identified highly conserved pathways regulating cell movement and polarity, wound healing, innate immunity and appendage formation. More recently, it has emerged that the establishment and repair of the barrier function of the integument are also achieved by common mechanisms involving genes responsible both for cross-linking surface proteins and for assembly of cellular tight junctions. These studies support the model that the formation and maintenance of the epidermal impermeable barrier in a wide range of species relies on two independent and complementary pathways.