Umami taste is elicited by many small molecules, including amino acids (glutamate and aspartate) and nucleotides (monophosphates of inosinate or guanylate, inosine 5'-monophosphate and guanosine-5'-monophosphate). Mammalian taste buds respond to these diverse compounds via membrane receptors that bind the umami tastants. Over the past 15 y, several receptors have been proposed to underlie umami detection in taste buds. These receptors include 2 glutamate-selective G protein-coupled receptors, mGluR4 and mGluR1, and the taste bud-expressed heterodimer T1R1+T1R3. Each of these receptors is expressed in small numbers of cells in anterior and posterior taste buds. The mGluRs are activated by glutamate and certain analogs but are not reported to be sensitive to nucleotides. In contrast, T1R1+T1R3 is activated by a broad range of amino acids and displays a strongly potentiated response in the presence of nucleotides. Mice in which the Grm4 gene is knocked out show a greatly enhanced preference for umami tastants. Loss of the Tas1r1 or Tas1R3 genes is reported to depress but not eliminate neural and behavioral responses to umami. When intact mammalian taste buds are apically stimulated with umami tastants, their functional responses to umami tastants do not fully resemble the responses of a single proposed umami receptor. Furthermore, the responses to umami tastants persist in the taste cells of T1R3-knockout mice. Thus, umami taste detection may involve multiple receptors expressed in different subsets of taste cells. This receptor diversity may underlie the complex perception of umami, with different mixtures of amino acids, peptides, and nucleotides yielding subtly distinct taste qualities.