Psychopharmacological drug manipulation creates causal mechanisms for selectively stimulating or blocking target neurotransmitter receptors known to modulate brain regions engaged in trust behavior. In this chapter, we review studies that used pharmacological agents to act as neuromodulators in the neural signaling pathway mechanisms underlying trust behavior. First, we describe the laboratory measurements of trust behavior, the underlying domain-general large-scale brain networks, and its related target neurotransmitter systems that probe trust behavior. Second, we review the psychopharmacological studies focusing first on studies that implemented the trust game and second on studies that applied trust ratings after cooperative exchange games. Overall, some preliminary evidence exists that neuromodulators such as opiates, monoamine neurotransmitters (e.g., serotonin, dopamine), and pharmacologic agents such as 3,4-Methyl-enedioxy-methamphetamine increase monoamine neurotransmitter activity and impact trust behavior via experimental paradigms that have face validity in laboratory measures of trust. Finally, we indicate shortcomings in the present psychopharmacological research approach and offer guidance for future interdisciplinary research on the neuropsychoeconomic underpinnings of trust –shedding light on trust impairment as a key feature of several neuropsychiatric disorders.