Abstract: A truly remarkable aspect of human existence is the unitary sense of self that exists across time and place. Understanding the nature of self—what it is and what it does—has challenged scholars since antiquity. How can empirical research measure what it is to have a sense of self? We propose that the sense of self may emerge from the functions of a left hemisphere “interpreter” (Gazzaniga, 2000). First, we examine evidence for the existence of self-processing mechanisms in the intact brain, from behavioral and functional neuroimaging research. The available evidence suggests that the sense of self is widely distributed throughout the brain. Second, we discuss these findings in relation to what is known about higher cognitive functions in humans who have undergone a surgical procedure to sever the connection between the two cerebral hemispheres. Split-brain research has facilitated an understanding of the way in which each cerebral hemisphere independently processes information. Research in this area has shown that each cerebral hemisphere features distinct information-processing capabilities. This cognitive asymmetry is reflected in the notion of a left hemisphere interpreter module which, we have argued, generates a unitary sense of consciousness even in the disconnected brain. This chapter describes how this interpreter may also give rise to a unified sense of self.