At various mucosal sites, such as in the eye and the respiratory and intestinal tracts, the immune system uses highly sophisticated and organized lymphoid tissues known as mucosa-associated lymphoid tissues (MALTs). Studies of the molecular and cellular basis of MALT organogenesis have provided evidence that MALTs are key sites for the induction of active immune responses for protection against pathogenic infections. These functions of the mucosal immune system are currently being used to develop mucosal vaccines, and accumulating evidence has recently indicated that targeting MALTs with vaccine antigens efficiently induces mucosal immunity. In this review, we describe the unique immunological functions of MALTs and the current and future directions of the development of mucosal vaccines.