The use of monoclonal antibodies has become routine in research and diagnostic laboratories but the potential level of antibodies in use in public health and medical applications is still far from its maximum. From a clinical perspective, topical immunotherapy of mucosal surfaces with monoclonal antibodies can block entry and transmission of bacteria, viruses, fungi and parasites that infect humans, and defeat some key strategies, evolved by many pathogens, to evade the host immune system. The chief antibody at mucosal surfaces is secretory immunoglobulin A (SIgA), a multi-polypeptide complex originating from two cell types. The recent design of heterologous expression systems, coupled with modern biotechnology processes, should form a sound basis for studying the functional properties of SIgAs and evaluate their value as biotherapeutics. Here, we discuss the principles underlying mucosal immunity and review the application of recombinant SIgA to the dissection of mechanisms in passive and active protection at mucosal surfaces.