The behavioral evidence for dopaminergic modulation of prefrontal cognitive functioning is reviewed. The experimental studies in rats, monkeys, and humans that highlight the inverted U-shaped relationship between dopamine and cognition are described and discussed in relation to theories of motivation and arousal. It is suggested that the disruptive effects of L-DOPA on reversal learning and decision making and the facilitatory effects of L-DOPA on task-switching and spatial working memory in patients with Parkinson’s disease support a role for dopamine in modulating both ventral and dorsolateral-striatal circuits. The fact that certain prefrontal tasks may be more sensitive to dopaminergic modulation than others is considered in the light of findings from 6-OHDA lesion studies in monkeys. A specific role for dopamine in protecting prefrontal processing from interference is shown by the marked disruption of marmosets with 6-OHDA lesions of the prefrontal cortex (PFC) in performing a visual discrimination in the presence of distracting stimuli. The finding that 6-OHDA lesions of the caudate nucleus protect the performance of marmosets from such distracting stimuli is discussed in relation to the possible competition and co-ordination of the PFC and caudate nucleus and emphasizes the need for any theory of dopamine function in the PFC to take into account the role of dopamine at the level of the striatum.