The buccal cavity is attractive for noninvasive, controlled transmucosal delivery of both local and systemic therapeutically active compounds. Administering drugs via this route is advantageous due to the rich vasculature of the oral mucosa, and the absence of gastrointestinal and “first-pass” hepatic degradation. Moreover, the barrier properties of the oral mucosa against noxious substances and its role in disease require further investigation. However, the scarcity of sizeable specimens of human oral mucosa for in vitro experimental studies has hampered research on this tissue. For this reason we developed a model in which human vaginal mucosa is used as a substitute for buccal mucosa. In this article the quality and predictive value of the human vaginal / buccal in vitro model with respect to a number of drugs and other chemical compounds differing widely in molecular size and lipophilicity, including water, arecoline, arecaidine, benzo[a]pyrene, 17β-estradiol, sumatriptan, vasopressin and dextrans, are reviewed. In addition some applications of the model for investigating the effect of areca nut extract on epithelial barrier properties, temperature effects on water and 17β-estradiol flux rates, and cyclosporin diffusion through mucosal membranes are described. The permeability characteristics of vaginal mucosa, as a model of buccal mucosa, are compared with those of other human tissue, including mucosae from the small intestine and colon.