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A significant advantage of nonhuman primate models is the ability to use drug\u2010na\u00efve subjects in longitudinal designs that document the neurobiological changes that are associated with chronic drug use. Moreover, experimental therapeutics can be evaluated in subjects with well\u2010documented histories of drug exposure. The<jats:italic>in vivo<\/jats:italic>distribution and pharmacokinetics of drug binding in brain have been related to the time\u2010course of behavioral effects associated with the addictive properties of stimulants. Importantly, the characterization of drug interactions with specific protein targets in brain has identified potential targets for medication development. Neuroimaging has proven especially useful in studying the dynamic changes in neuronal function that may be associated with environmental variables. Last, neuroimaging has been used effectively in nonhuman primates to characterize both transient and long\u2010lasting changes in brain chemistry associated with chronic drug exposure. Although there is some evidence to suggest neurotoxicity in humans with long histories of stimulant use, parallel studies in nonhuman primates have not identified consistent long\u2010term changes in such neurochemical markers. 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