This article is available online at http://www.jlr.org the fi ve taste qualities, sweet, umami, salty, sour, and bitter ( 2 ). In the past, the existence of additional taste modalities such as fatty ( 3 ), metallic ( 4 ), or a taste for water ( 5 ) has been speculated. In recent years, particular attention has been paid to the potential existence of fat taste and its putative status compared with the other well-accepted taste qualities . Whereas the textural, olfactory, and postingestive recognition of fat constituents have been considered the dominant cues for fat perception in the past, several recent studies, performed mostly in rodents but also in humans, have pointed to a gustatory component in fat perception [for a recent review see ( 6 )]. The use of anosmic ( 7 ) or esophagostomized ( 8 ) rat models in combination with texture-masking buffer compositions indicated an orosensory detection mechanism for long-chain fatty acids, in particular. Moreover, a number of candidate receptors for the oral detection of lipophilic molecules were identifi ed by several independent research groups. These putative fat sensors include potassium channels ( 3 ) and scavenger receptor/fatty acid transporter CD36/FAT ( 9, 10 ), as well as G protein-coupled receptors (GPRs) such as GPR40 ( 11 ) and GPR120 ( 11-13 ). For some of the candidate receptors, knockout mouse models were analyzed and their contribution to orosensory fat perception confi rmed. Mice with a genetic ablation of CD36 exhibit no preference for the polyunsaturated long-chain fatty acid, linoleic acid, in two-bottle preference tests compared with wild-type mice. Moreover, a reduced cephalic phase response upon oral stimulation with oleic, linoleic, and linolenic acid, but not to the saturated long-chain fatty acid, stearic acid, or the medium-chain fatty acid, caprylic acid, suggests pronounced selectivity for particular lipophilic stimuli ( 10 ). Similarly, GPR40 as well as GPR120 knockout mice both show a loss of preference for linoleic acid, and The perception of taste elicited by countless chemicals present in food plays an important role for the survival of organisms. The gustatory system monitors not only the caloric content and the appropriate electrolyte supply, but also the presence of putatively harmful substances in food items ( 1 ). Detection of food constituents within the oral cavity is achieved by taste receptor molecules expressed by sensory cells specifi cally devoted to the detection of one of