This paper reviews the effects of a diverse range of penetration enhancers, including fatty acids, bile salts, surfactants, Azone® and ethanol, on oral mucosa. We describe in detail the effects on the intercellular lipid domains, the changes induced in proteinaceous regions and potential interactions between the enhancer and endogenous structures along the transport pathway. Since there have been few structure-based studies of the oral mucosa, which have discussed enhancer effect as a function of specific physicochemical properties, we have drawn upon analogous studies of skin and other mucosal membranes, as well as model lipid systems, e.g. liposomes.