Abstract: Trace amines—low-molecular-weight endogenous compounds structurally similar to monoamine neurotransmitters—were long considered mere byproducts of amino acid metabolism. However, the 2001 discovery of a family of specific receptors coupled with G proteins and trace amine-associated receptors (TAARs) prompted a reevaluation of their role in regulating physiological processes. This review outlines key milestones in the study of trace amines and their receptors, with particular emphasis on the contribution of animal genetic models. These models have been instrumental both in identifying physiological processes involving trace amines and in elucidating the molecular mechanisms underlying their action.