A review of the literature investigating the neural origins of detection behavior in humans reveals two event-related potential components, P3a and P3b, each with a distinct neural organization and cognitive function.The P3a is involved in automatic novelty detection and characterized by a more anterior cortical distribution, whereas the P3b is concerned with volitional target detection and has a more posterior cortical distribution. Intracranial investigation, studies with patients with focal brain lesions, and functional neuroimaging (fMRI) studies converge with scalp-recorded event-related potential (ERP) data in suggesting that a widespread cortical network gives rise to both automatic and controlled detection behavior. The main regions consistently attributed to generating detection-related brain activation include the temporal-parietal junction, medial temporal complex, and the lateral prefrontal cortex. The extant human and animal literature addressing the neural networks, neuropharmacological underpinnings, and behavioral significance of the P300 potential will be reviewed.