The aim of this chapter is, first, to analyse the specific articulation, in Plotinus, of the notions of self-knowledge, self-consciousness, and interiority. It is, more precisely, to show how the conceptual relations we have inherited from the ‘Cartesian moment’––between self-knowledge and self-consciousness, but also between self and substance, or between self and identity—are actually dissociated in Plotinus ‘philosophy. Insofar as he accepts an immediate reflexivity, Plotinus cannot be enlisted for the ancient thought of the self. But because he does not confer on self-knowledge the value of a principle, he cannot be enlisted either for the modern philosophies of consciousness and the subject. Nonetheless, Plotinus’ philosophy of the self was a direct source of inspiration for a Modern, the Cambridge Platonist Ralph Cudworth, who finds in it a basis to criticize some fundamental aspects of Descartes’ thought. The chapter therefore also evaluates this legacy.