In many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs), determine odor detection thresholds of mice to amines. We ﬁnd that deleting all TAARs, or even single TAARs, results in signiﬁcant odor detection deﬁcits. This ﬁnding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, increasing the number of sensory neurons (and glomeruli) expressing a threshold-determining TAAR does not improve detection, indicating that sensitivity is not limited by the typical complement of sensory neurons. Our ﬁndings demonstrate that olfactory thresholds are set by the single highest afﬁnity receptor and suggest that TAARs are evolutionarily conserved because they determine the sensitivity to a class of biologically relevant chemicals.