The Self is an interdisciplinary topic encompassing neuroscience, psychology, philosophy, and anthropology. Despite the wealth of data available on the topic, its definition remains elusive, while its meaning overlaps with terms such as consciousness, Ego, and I, and so has created more confusion and redundancy rather than clarity. Its study is also endowed with deep epistemological and metaphysical implications, on which the accepted axioms, theories, and method of investigation closely depend. Eastern philosophies have faced the problem of self-knowledge for some three millennia, achieving well-founded and valuable knowledge through introspection and meditation, and their results are worth being appraised in the Western, scientific study of the Self. We propose that the Self is related to the highest level of awareness in the continuum Ego-I-Self and, given its exclusively subjective nature (likewise consciousness), it can only be comprehensively explored through a neurophenomenological approach by merging the first and third person perspectives. Public Significance Statement This article approaches the Self through a metaphilosophical perspective encompassing both psychology and Western and Eastern philosophies, with the aim of moving beyond the constraints of a single, limited paradigm and cultural perspective. A proper comprehension of the Self-which remains elusive, despite having been investigated for centuries-is essential for philosophy, psychology, and neurosciences, as well as for everyday life in its personal, sociocultural, and political dimensions, being at the foundation of the Weltanschauung (the view of the world)-that is, what we are, or believe to be, and the still unsolved problem of the mind-brain-body-outer world relationship. Missing the highest expressions of the Self (as done by the ruling materialist monist perspective of science and the Ego dictatorship of the today world) entails a scientific and cultural mutilation of human mind, with devastating consequences for both the individual and the social life.