The mammalian gastrointestinal tract can harbor both beneficial commensal bacteria important for host health, but also pathogenic bacteria capable of intestinal damage. It is therefore important that the host immune system mount the appropriate immune response to these divergent groups of bacteria-promoting tolerance in response to commensal bacteria and sterilizing immunity in response to pathogenic bacteria. Failure to induce tolerance to commensal bacteria may underlie immune-mediated diseases such as human inflammatory bowel disease. At homeostasis, regulatory T (Treg) cells are a key component of the tolerogenic response by adaptive immunity. This review examines the mechanisms by which intestinal bacteria influence colonic T-cells and B-cell immunoglobulin A (IgA) induction, with an emphasis on Treg cells and the role of antigen-specificity in these processes. In addition to discussing key primary literature, this review highlights current controversies and important future directions.