Purpose of review. Oral immunization with vaccines against intestinal infectious diseases has been extensively explored for several decades. Despite the immunologic and economic rationale behind oral immunization, only a few mucosal vaccines are available for the prevention of mucosal infections. Here, we summarize the current status of such vaccines, with a focus on intestinal infectious diseases, describe alternative approaches, and analyze advantages and difficulties encountered with a broad implementation of these vaccines. Recent findings. Due to the limited absorption from the intestinal tract and sensitivity to degradation, oral vaccines composed of killed bacteria and viruses or antigens isolated from infectious agents have not been successful. New, live-attenuated bacterial and viral or edible plant-derived vaccines, however, have been recently introduced for this purpose. Furthermore, systemic immunization with vaccines composed of bacterial polysaccharides chemically coupled to suitable protein carriers induces high levels of IgG antibodies, which may provide immunity toward Salmonella typhi, Shigella, and Escherichia coli. Summary. Further improvements in antigen-delivery systems, the development of adjuvants that are safe for mucosal application in humans, use of live-attenuated vaccines and microbial vectors, and production of certain vaccines in plant expression systems are likely to contribute to the broader use of oral vaccines in the future. © 2008 Welters Kluwer Health|Lippincott Williams & Wilkins.