Septate junctions (SJs) are specialized intercellular junctions that function as permeability barriers to restrict the free diffusion of solutes through the paracellular routes in invertebrate epithelia. SJs are subdivided into several morphological types that vary among different animal phyla. In several phyla, different types of SJ have been described in different epithelia within an individual. Arthropods have two types of SJs: pleated SJs (pSJs) and smooth SJs (sSJs), found in ectodermally and endodermally derived epithelia, respectively. Several lines of Drosophila research have identified and characterized a large number of pSJ-associated proteins. Two sSJ-specific proteins have been recently reported. Molecular dissection of SJs in Drosophila and animals in other phyla will lead to a better understanding of the functional differences among SJ types and of evolutionary aspects of these permeability barriers.