Having an understanding of ourselves has been a fundamental topic for psychologists, philosophers, and laypeople alike since the beginnings of consciousness. Whether one’s own sense of self has any special neurocognitive status has been hotly debated. This chapter reviews neuropsychological and neuroimaging evidence that argues for the special status of self-knowledge in memory. The contributing roles to self-knowledge of central nodes in the brain’s default mode network of regions are also discussed. This review argues that these nodes may be functionally dissociated along multiple lines, with an important dissociation concerning the representation of psychological characteristics and the representation of physical characteristics. It is also argued that the medial prefrontal cortex, a critical node in the default mode network, enjoys anatomical and functional connectivity that together suggest a role for it in delineating the world into “me” and “not me.” The chapter concludes with suggested lines of future inquiry that might provide more direct evidence of this role.