Distortions of self-experience are a central feature of many altered states of consciousness, from acute psychosis to the psychedelic experience and states of mystical consciousness. In psychedelic states a reduction in the normally well-circumscribed experience of self has been termed ‘drug-induced ego-dissolution’ (DIED), and is related to a feeling of increased unity with others and one’s surroundings. DIED is of relevance both for a study of the neurophysiological correlates of self-experience, and for philosophical discussions about self-awareness. In recent years several studies have attempted to investigate the neurophysiological correlates of DIED occasioned by classical psychedelic drugs, using non-invasive neuroimaging. Although these studies are limited by their ability to validly quantify the subjective experience of DIED, they reveal that this experience is associated with a decrease in the integrity of resting-state brain networks associated with the sense of self, and may occasion a more ‘globally unified’ mode of brain function. These changes may be of therapeutic relevance. DIED is also of relevance to philosophical discussions about self-awareness. Questionnaire data and narrative reports are consistent in suggesting that the phenomenology of ego dissolution involves the loss of one’s sense of self, to the extent that some subjects are even reluctant to use the first-person pronoun to describe their experience. This preliminary evidence suggests that ego dissolution does not merely disrupt the ‘narrative self’, one’s network of autobiographical memories and self-related beliefs, but also disrupts the low-level multisensory aspects of selfhood, termed the ‘minimal self’. This challenges the widely held notion that a minimal form of self-awareness accompanies all conscious states, although ordinary experience may involve such self-awareness. These empirical and theoretical advances provide a tantalizing insight into the neuronal mechanisms underpinning the normal experience of a coherent and well-circumscribed ‘self’, and inform philosophical discussions on the nature of self-awareness.