The epithelia lining the ducts of exocrine glands and the gastrointestinal, the respiratory and the urogenital tracts represent the largest organ system (400 m2 in humans) in upper vertebrates. Immunity at the mucosal surfaces, which are the port of entry for many pathogens, is essential in preventing infection. In order to protect these very thin and sensitive surfaces, the body has evolved an elaborated set of mechanisms that prevent attachment, colonization and possible damage by pathogenic agents. Specific antibody responses in mucosal tissues is typified by secretory immunglobulin A, the predominant Ig class in human secretions, and the best known entity providing specific immune protection for mucosal tissues. This chapter will focus on the general mechanisms required to achieve an efficacious mucosal immune response, on the structure-function relationship in S-IgA, on the molecular engineering of recombinant S-IgA, and on how these molecules have helped to elucidate cellular mechanisms crucial to mucosal immunity.