Psychophysiological measures hold great potential for informing clinical assessments. The challenge, before such measures can be widely used, is to develop test procedures and analysis strategies that allow for statistically reliable and valid decisions to be made for any particular examinee, despite large individual differences in psychophysiological responding. Focusing on the evaluation of memory in clinical, criminal, and experimental contexts, this paper reviews the rationale for and development of ERP-based memory assessment procedures, with a focus on methods that allow for statistically supported decisions to be made in the case of a single examinee. The application of one such procedure to the study of amnesia in Dissociative Identity Disorder is highlighted. To facilitate the development of other psychophysiological assessment tools, psychophysiological researchers are encouraged to report the sensitivity and specificity of their measures where possible.