Trace amines, including β-phenylethylamine (β-PEA), p-tyramine (TYR), tryptamine (TRP), and p-octopamine (OCT), represent a group of amines expressed at low levels in the mammalian brain. Given the close structural similarities to traditional monoamines, links between trace amines and the monoaminergic system have long been suspected. Trace amine-associated receptor 1 (TAAR1), the most well characterized receptor in the TAAR family, has been shown to be potently activated by trace amines such as TYR and PEA. Further, catecholamine metabolites and amphetamine analogs are also potent agonists of TAAR1, implicating the receptor in mediating the monoaminergic system and in substance use disorders. In the central nervous system, TAAR1 is expressed in brain regions involved in dopaminergic, serotonergic, and glutamatergic transmission, and genetic animal models and electrophysiological studies have revealed that TAAR1 is a potent modulator of the monoaminergic system. Selective and potent engineered TAAR1 ligands, including full (RO5166017 and RO5256390) and partial (RO5203648, RO5263397 and RO5073012) agonists and the antagonist EPPTB (N-(3-ethoxyphenyl)-4-(1-pyrrolidinyl)-3-(trifluoromethyl) benzamide, RO5212773), serve as invaluable tools for the investigation of TAAR1 functions and display significant potential for the development of TAAR1-based pharmacotherapies for the treatment of substance use disorders. Despite a number of advances that have been made, more clinical studies are warranted in order to test the potential and efficacy of TAAR1 ligands in the treatment of psychiatric disorders, including substance use disorders.