Infectious diseases continue to be the leading cause of morbidity and mortality worldwide. Increased awareness of the fact that mucosal membranes are the most frequent portals of entry of pathogenic microorganisms has prompted studies aimed at the development of vaccination protocols and antigen delivery systems that would lead to an increased protection of mucosae. Although systemic and strictly local (e.g., intravaginal or conjunctival) immunizations are of limited effectiveness in the induction of generalized mucosal protection, ingestion or inhalation of antigens results in a disseminated immune response manifested by the appearance of specific antibodies of the secretory immunoglobulin (Ig) A isotype in external secretions due to the dissemination of IgA precursor cells from IgA-inductive lymphoid tissues. Furthermore, additional inductive sites strategically positioned at the opening of the respiratory and digestive tracts may also be suitable targets for induction of immune responses at desired effector sites. To prevent degradation and increase the absorption of ingested antigens, novel strategies including enclosure of antigens in biodegradable microspheres or liposomes, or their expression in viral and bacterial vectors and in plants, are currently being considered. Forthcoming technological advances in antigen preparation and routes of delivery will undoubtedly have a profound impact on immunization practices in the future.