An ideal vaccine ought to produce long-term protective immune responses against a pathogen. These responses include humoral antibodies, which neutralize invasive microorganisms, and cytotoxic T cells, which destroy intracellular pathogens. Both types of responses can be induced by parenteral immunization, which is how most vaccines have been administered to date. Given that most bacteria and viruses initiate infections at mucosal surfaces where secretory immunoglobulin A (sIgA) antibodies are thought to play an important role in prevention of microbial attachment and colonization, there may be an added advantage for vaccines that stimulate long-lasting secretory immunity against pathogens as well. A prerequisite for the generation of sIgA antibodies is that antigens be delivered at mucosal sites. This review focuses on novel mucosal vaccination strategies aimed at inducing such secretory immunity to pathogens, while at the same time, stimulating humoral and, in some cases, cellular immunity.