The commensal microbiota, most of which resides in the gut, is an environmental regulator of mucosal and systemic immune maturation. Epidemiological studies suggest that changes in the microbiota may represent a link between a modern lifestyle and risk of certain immuno-allergic diseases. This suggests that the microbiota is an appropriate target for therapy or prophylaxis, the rationale for which is addressed here using inflammatory bowel disease as an example. It is also evident from comparative studies of germ-free and conventionally colonized animals that the microbiota is a source of regulatory signals for full development of the host. In some instances these signals have been defined molecularly, and may be suitable for exploitation in novel drug discovery. Most of the versatile drugs in common usage today were derived originally from living matter in the wider environment; could it be time to mine new drugs from microbial-derived signalling molecules in the inner environment of the gut? Several examples illustrate the potential of the gut microbiota as a rich repository from which bioactives with immunological impact can be mined, and translated to human health care or to animal husbandry.