This chapter focuses on the interaction of viruses with epithelial cells. The role of specific pathways of virus entry and release in the pathogenesis of viral infection is examined together with the mechanisms utilized by viruses to circumvent the epithelial barrier. Polarized epithelial cells in culture, which can be grown on permeable supports, provide excellent systems for investigating the events in virus entry and release at the cellular level, and much information is being obtained using such systems. Much remains to be learned about the precise routes by which many viruses traverse the epithelial barrier to initiate their natural infection processes, although important information has been obtained in some systems. Another area of great interest for future investigation is the process of virus entry and release from other polarized cell types, including neuronal cells.