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Selfhood and self-awareness, at least in humans, can be dissected into many levels. At one level, self-awareness describes a metacognitive aspect of consciousness wherein higher-order thought is directed through attentional focus on the self-object and self-related matters. This chapter explores the insights gained from neuroimaging studies into the brain substrates and mechanisms underlying such “high-level” self-referential processing. At another level, selfhood is reflected in self-recognition processes which discriminate self-related stimuli from other similar stimuli. Here, we examine the relevant neuroimaging evidence, focusing on self-face recognition as an exemplar. At a more fundamental level, we review what is known about the mental representation of the body, focusing on studies suggesting that a primary sense of self is ultimately derived from the neural representation of the body via interoception. These studies emphasize the continuous mapping of dynamic changes in internal state, whereby physiological demands and homeostatic imperatives dictate motivations and shape the contents of cognition. Here, converging neuroimaging evidence suggests that brain regions involved in representing internal physiological processes and making them available to conscious appraisal contribute to self-referential cognitions. This link is further apparent in the neural correlates of cognitive control and detachment techniques, such as mindfulness, that increasingly find clinical utility. Ultimately, inferences from neuroimaging regarding selfhood and self-awareness must cohere with evidence from lesion studies and with an increasingly sophisticated understanding of the brain as a connected network generating self-representations via a range of overlapping mechanisms.