Legally relevant lying is an intentional attempt to convince another of the truth of a proposition the liar believes to be false. Delusion is an unintentional product of impaired reality testing that occurs in a range of psychiatric conditions and psychological states, some of which could be clinically subtle, since deception, truth and delusion differ in the intent rather than reality testing criterion. Deception and delusion are influenced by the degree of congruence between subjective and objective reality and are probably mutually exclusive. Thus, a delusion could lead to an objectively false statement, that could nevertheless be subjectively true and indistinguishable from truth by its psychophysiological (i.e., the polygraph) signature. This article presents a relevant case as a starting point of an examination of the current and future role of neurophysiological (i.e., functional brain imaging) measurements in the detection of deception. The authors incorporate the recent data on functional brain imaging to the neuroanatomical mechanisms of true and false recall, behavioral regulation and deception into a testable model that could redefine deception and separate it from delusions on the basis of objective functional brain imaging measures.