Mucosal immunity covers a variety of mucosal surfaces susceptible to different pathogens. This review highlights the diversity of mucosal tissues and the unique microenvironments in which an immune response is generated. It argues that tissue-specific factors present throughout mucosal tissues and lymph nodes determine the differentiation into IgA-producing B cells, which in turn determines their migration patterns. Mucosal immunity can therefore be induced when antigen is delivered at any mucosal tissue without the need for specific mucosal adjuvants or targeting to specialised lymphoid structures. Non-oral vaccination strategies directed at alternative and more accessible mucosal tissue sites, may provide new avenues for both mucosal and systemic immunization, and will be greatly facilitated by the use of large animal models.