We investigated the extent to which a common neural mechanism is involved in task set-switching and response withholding, factors that are frequently confounded in taskswitching and go/no-go paradigms. Subjects' brain activity was measured using event-related electrical potentials (ERPs) and event-related functional MRI (fMRI) neuroimaging in separate studies using the same cognitive paradigm. Subjects made compatible left/right keypress responses to left/right arrow stimuli of 1000 msec duration; they switched every two trials between responding at stimulus onset (GO task—green arrows) and stimulus offset (WAIT task—red arrows). Withholding an immediate response (WAIT vs. GO) elicited an enhancement of the frontal N2 ERP and lateral PFC activation of the right hemisphere, both previously associated with the “nogo” response, but only on switch trials. Task-switching (switch vs. nonswitch) was associated with frontal N2 amplification and right hemisphere ventrolateral PFC activation, but only for the WAIT task. The anterior cingulate cortex (ACC) was the only brain region to be activated for both types of task switch, but this activation was located more rostrally for the WAIT than for the GO switch trials. We conclude that the frontal N2 ERP and lateral PFC activation are not markers for withholding an immediate response or switching tasks per se, but are associated with switching into a response-suppression mode. Different regions within the ACC may be involved in two processes integral to task-switching: processing response conflict (rostral ACC) and overcoming prior response suppression (caudal ACC).