Immunoglobulin A is the main element of the humoral immune response that has been selected through evolution, together with innate mucosal defences, to provide protection against microbial antigens at mucosal surfaces. IgA responses are initiated in organized inductive structures, such as Peyer's patches and nasal-associated lymphoid tissues, as well as diffuse effector tissues, such as gut lamina propria and nasal mucosa. Hypermutated secretory IgAs play a critical role in regulating the composition of the intestinal microflora. Dysregulation of gut homeostasis in IgA-deficient gut causes a continuous activation of the immune cells and induces inflammatory processes leading to lymphoneogenesis. Recent advances in this field include new insights into the role of IgA in the maintenance of gut homeostasis and the proposal of an updated model for the induction of IgA responses in the gut.