BAIT AND SWITCH: Metabolite-sensing riboswitches make use of RNA structural modulation to regulate gene expression, as illustrated in the scheme, in response to subtle changes in metabolite concentrations. This review describes the current knowledge about naturally occurring riboswitches and their growing potential as antibacterial cellular targets and as molecular biosensors. Newly discovered metabolite-sensing riboswitches have revealed that cellular processes extensively make use of RNA structural modulation to regulate gene expression in response to subtle changes in metabolite concentrations. Riboswitches are involved at various regulation levels of gene expression, such as transcription attenuation, translation initiation, mRNA splicing and mRNA processing. Riboswitches are found in the three kingdoms of life, and in various cases, are involved in the regulation of essential genes, which makes their regulation an essential part of cell survival. Because riboswitches operate without the assistance of accessory proteins, they are believed to be remnants of an ancient time, when gene regulation was strictly based on RNA, from which are left numerous "living molecular fossils", as exemplified by ribozymes, and more spectacularly, by the ribosome. Due to their nature, riboswitches hold high expectations for the manipulation of gene expression and the detection of small metabolites, and also offer an unprecedented potential for the discovery of novel classes of antimicrobial agents.