Neuropsychological studies indicate the presence of cognitive changes in patients with obsessive-compulsive disorder (OCD). Indeed, OCD may be included among the dysfunctions of the frontal lobes and their connections with the limbic system, associative cortex, and basal ganglia. P300 is a positive component of the human event-related potential (ERP); it is associated with processes of encoding, identification, and categorization constituting, as a whole, the superior cortical function of information processing. Thus, P300 explores several areas that are implicated in OCD pathophysiology. Our aim is to review all relevant studies on the P300 component of the human ERP in order to recognize any significant central nervous system (CNS) correlate of cognitive dysfunction in OCD. A PubMed-based literature search resulted in 35 articles assessing P300 in OCD and reporting neurophysiological correlates of response inhibition, cortical hyperarousal, and over-focused attention. A decreased P300 amplitude was reported in both adult and pediatric patients, with a trend toward normalization after pharmacological treatment. Source localization studies disclosed an association between P300 abnormalities and the functioning of brain regions involved in the pathophysiology of OCD. Moreover, studies converge on the evidence of neurophysiological dysfunction in the frontal areas with impairment of the normal inhibitory processes in OCD. At least some of these electrophysiological correlates might reflect the obsessive thoughts and compulsions that characterize this disorder. These findings may also support cognitive-behavioral therapy (CBT) approaches on over-focused attention and inflexibility of compulsive behaviors, which should be associated to pharmacological treatment in these patients.