The P300 event-related brain potential (ERP) has been used to study normal aging as well as patient populations with a variety of neurologic and psychiatric disorders. The P300 has demonstrated reasonable success as a means to assess disturbances in cognitive function, and its clinical utility has been enhanced by the identification of factors that contribute to the variability of ERP measurements. In this article, the neuropsychological theory of P300 is reviewed, ways in which this brain potential can be used as a measure of cognitive efficiency are defined, and methodologic issues that must be considered for successful clinical ERP applications are outlined. This approach is then extended to specific recommendations concerning the technical and practical aspects of P300 recording, so that a well-defined normative database can be developed for evaluating individual patients. When appropriate procedures are used, the P300 can provide a highly useful means to quantify human cognitive capability.