The bitter taste receptor (TAS2R)-family of G-protein-coupled receptors has been identified on the tongue as detectors of bitter taste over a decade ago. In the last few years, they have been discovered in an ever growing number of extra-oral tissues, including the airways, the gut, the brain and even the testis. In tissues that contact the exterior, protective functions for TAS2Rs have been proposed, in analogy to their function on the tongue as toxicity detector. However, TAS2Rs have also been found in internal organs, suggesting other roles for these receptors, perhaps involving as yet unidentified endogenous ligands. The current review gives an overview of the different proposed functions for TAS2Rs in tissues other than the oral cavity; from appetite regulation to the treatment of asthma, regulation of gastrointestinal motility and control of airway innate immunity.