Over the past few decades, advancements in molecular and cell biology have allowed scientists to identify a large number of new antigens from a variety of viral and bacterial pathogens. However, successful development of these antigens into effective vaccines strongly relies on delivery systems able to avoid the rapid loss of biological activity that often impairs antigen efficacy. Various delivery systems have been proposed as alternative vaccine vehicles, from live microorganisms to nanoparticles, and all of them have shown advantages but also drawbacks. The bacterial spore is a quiescent cell form that, as a vaccine vehicle, may conjugate some advantages of live microorganisms with those of synthetic nanoparticles and that has recently been proposed as a potentially powerful tool to deliver antigens to mucosal surfaces. Here we review the use of bacterial spores as a delivery system for mucosal immunizations. We will first analyze the nature of the interaction between wild type spores and the gut-associated lymphoid tissue and then address the immune responses that are induced by oral immunizations with recombinant spores displaying heterologous antigens.