The majority of activated B cells differentiate into IgA plasma cells, with the gut being the largest producer of immunoglobulin in the body. Secretory IgA antibodies have numerous critical functions of which protection against infections and the role for establishing a healthy microbiota appear most important. Expanding our knowledge of the regulation of IgA B-cell responses and how effective mucosal vaccines can be designed are of critical importance. Here we discuss recent developments in the field that shed light on the uniqueness and complexity of mucosal IgA responses and the control of protective IgA responses in the gut, specifically.