The aim of this paper is to review the lipid composition of different regions of the oral mucosa, bearing in mind that, in general, molecular diffusion occurs through the intercellular lipids. Lipid content and organization is described to explain the permeability differences between keratinized and nonkeratinized tissues. Some of the thermotropic and lyotropic transitions observed in simple lipid model systems, such as liposomes, are also taken into consideration, in an attempt to explain the contribution of each lipid class to the permeability barrier.