Mucosa-associated lymphoid tissue in the respiratory and digestive tracts are covered by a specialized epithelium, the follicle-associated epithelium, which includes M cells, which are specialized for the uptake and transcytosis of macromolecules and microorganisms. Following transcytosis, antigens are released to cells of the immune system in lymphoid aggregates beneath the epithelium where antigen processing and presentation and stimulation of specific B and T lymphocytes are achieved. Circulation of the lymphoid cells enables their homing to their original, and other, mucosal sites where they exert the effector function. Such a response may be dominated by secretory immunoglobulin A release and may include cytotoxic T lymphocyte action. Binding of particles to the apical M cell membrane may be nonspecific or due to specific interaction between molecules such as integrins and lectins. Exploiting the specific binding to M cells is an aim for mucosal vaccination, for example to increase the efficiency of uptake of an oral vaccine by its conjugation to an M-cell-specific molecule. Alternatively, an M-cell-specific live vector, such as attenuated Salmonella bacteria, may be used to deliver epitopes of other organisms. Mucosal vaccination efficiency may also be enhanced by a temporary increase in the number of M cells. Therefore, investigation of the properties and ontogeny of M cells must be pursued to allow the development of better mucosal vaccines for the future.