A fundamental role of the mammalian immune system is to eradicate pathogens while minimizing immunopathology. Instigating and maintaining immunological tolerance within the intestine represents a unique challenge to the mucosal immune system. Regulatory T cells are critical for continued immune tolerance in the intestine through active control of innate and adaptive immune responses. Dynamic adaptation of regulatory T-cell populations to the intestinal tissue microenvironment is key in this process. Here, we discuss specialization of regulatory T-cell responses in the intestine, and how a breakdown in these processes can lead to chronic intestinal inflammation.