This article addresses the centuries old but recently revived topic of human autonomy and its relation to people’s functioning: physiological, psychological, and socio-cultural. It provides a review of current debates about status, nature, and perspectives of studying autonomy, agency, free will and self-determination in neuro- and cognitive sciences, motivation, personality and cultural psychology. This review starts with the theoretical definitions of the concepts and differentiates personal, intrapsychic, and motivational autonomy as well as behavioral freedom; delineates the distinction between autonomous and controlled forms of human agency; and relates all these concepts to the notion of human happiness and optimal functioning. It supports the idea of the universality of psychological autonomy as a fundamental capability of human species and argues that this capability is a real natural power that does not contradict the principle of determinism. Special attention is paid to the debates about the role culture plays in enabling and regulating human autonomy. The idea of dialectical relations between culture and human autonomy is presented and defended.