Mucosal vaccine delivery potentially induces mucosal as well as systemic immune responses and may have advantages particularly for optimal protection against pathogens that infect the host through mucosal surfaces. However, the delivery of antigens through mucosal membranes remains a major challenge due to unfavorable physiological conditions (pH and enzymes) and significant biological barriers, which restrict the uptake of antigens. To improve mucosal vaccine delivery, the use of bioadhesive delivery systems offers numerous advantages, including protection from degradation, increasing concentration of antigen in the vicinity of mucosal tissue for better absorption, extending their residence time, and/or targeting them to sites of antigen uptake. Although some bioadhesives have direct immune stimulating properties, it appears most likely that successful mucosal vaccination will require the addition of vaccine adjuvants for optimal immune responses, particularly if they are to be used in an unprimed population. Thus, complex vaccine formulations and delivery strategies have to be carefully designed to appropriately stimulate immune response for the target pathogen. In addition, careful consideration is needed to define the "best" route for mucosal immunization for each individual pathogen.