Abstract The field of opioid research took a large step forward with the development of technology that permitted the demonstration of opiate receptors in the brain in the early 1970s. This then led rapidly to the discovery of endogenous biologic peptides with opiate activity. Simon 1 has coined the term “endorphin” to designate this new and exciting group of brain substances, and today there is much speculation that the endorphins may have a significant role to play in clinical psychiatry of the future. Early interest had been alerted by several striking findings from studies in opioid pharmacology that suggested that this group of compounds exerted their pharmacologic activities via specific receptors: 2 namely, (1) astonishingly low doses of opiates put forth detectable pharmacologic action and etorphine, a morphinomimetic agent, (2) can exert a 5,000-to-10,000-times more potent action than morphine; (3) only the levoisomer of morphine is pharmacologically active indicating stereospecificity; 3 and (4) pure opium antagonists that produce neither euphoria nor analgesia are available. By 1973, workers 4–7 from several major centers around the world demonstrated the existence of specific opiate receptor binding sites on cell membranes, and a competitive race had begun to find those substances now called the endorphins.