Fatty foods are very palatable. Most mammals, including humans, prefer high-fat food to low-fat food. Neuropeptides and neurotransmitters, which are related to the hedonic or aversive response in the brain, are released after a basic tastant (i.e., sweet, sour, salty, bitter or umami) is accepted by the taste receptors in the taste bud cells. In addition, recent evidence suggests that dietary fat, especially free fatty acids, may be perceived chemically in taste bud cells as well as the basic tastant. Recently, it was suggested that long-chain fatty acids accepted into CD36/FAT, a long-chain fatty acid transporter, in circumvallate papillae of the tongue play an extremely important role in the palatability of dietary fat. In this review, we describe the studies on the reception of fatty acids in the oral cavity, and on the signal transmission from the oral cavity to the brain. We hypothesize that long-chain fatty acids are recognized on the tongue, and then neuropeptides and neurotransmitters such as beta-endorphin and dopamine are released in the brain. We suggest that this knowledge is one of the mechanisms of the palatability of dietary fat.