Abstract Animals reject diets that lead to indispensable amino acid (IAA) depletion or deficiency. This behavior is adaptive, as continued IAA depletion is incompatible with maintenance of protein synthesis and survival. Following rejection of the diet, animals begin foraging for a better IAA source and develop conditioned aversions to cues associated with the deficient diet. These responses require a sensory system to detect the IAA depletion and alert the appropriate neural circuitry for the behavior. The chemosensor for IAA deprivation is in the highly excitable anterior piriform cortex (APC) of the brain. Recently, the well-conserved general AA control non-derepressing system of yeast was discovered to be activated by IAA deprivation via uncharged tRNA in mammalian APC. This system provides the sensory limb of the mechanism for recognition of IAA depletion that leads to activation of the APC, diet rejection, and subsequent adaptive strategies.