M cells are epithelial cells specialized for sampling viruses and bacteria and perform a critical role in immune surveillance in mucosal tissues. The M cell apical surface is modified with less frequent microvilli and a thinner glycocalyx, and the basolateral membrane is invaginated to form an intraepithelial 'pocket' enclosing leukocytes. These alterations facilitate endocytosis and phagocytosis of microorganisms and transport across the epithelium. In certain tissues, M cell apical membranes exhibit distinct receptors which have been identified with monoclonal antibodies and lectins. Pathogenic bacteria and viruses can recognize the M cell surface and exploit its transcellular transport pathway to gain entry into host tissues. M cells sample and transport synthetic microspheres in a manner similar to microorganisms and thus play an essential role in the delivery of vaccines and drugs to mucosal lymphoid tissues. However, the efficiency of sampling orally delivered microparticles by M cells is low. Strategies are being developed to target microparticles to M cell apical surfaces using M cell-selective probes in order to increase sampling efficiency and bioavailability of drugs and vaccines. Such targeting strategies will likely be critical for the development of more effective vaccines and drugs administered by mucosal routes.