Cholecystokinin (CCK) coexists with dopamine in a large proportion of the ventral tegmental and substantia nigra neurons in rodents and primates. In this review Jacki Crawley integrates the neurophysiological, behavioral, and release studies which demonstrate both excitatory effects of CCK, and facilitatory modulating effects of CCK on the inhibitory actions of dopamine, in the mesolimbic pathway. Nonpeptide antagonists selective for the CCKA and CCKB receptors have recently been developed, and provide long-awaited tools to test hypotheses about the role of endogenous CCK as a modulator of dopaminergic function, and the potential of CCK-based drugs as treatments for neuropsychiatric disorders.