This article examines and refutes the claims that neuroscientific evidence renders autonomy “quixotic” and thus supports a shift toward paternalism in medical and political decision-making. The author argues that the notion of autonomy has been mistakenly associated with the metaphysical concept of free will, and offers a political definition of autonomy to clarify how responsibility is implicitly grounded in the legal and political system: An agent acts autonomously when she/he (a) endorses decisions and acts in accord with internal motivational states, (b) shows commitment to them in the absence of undue coercion and compulsion, and (c) could as a reasonable and rational person continue to do so after a period of informed critical reflection. The author further argues that neuroscientific findings confirm the assumption that humans are fundamentally fallible social creatures and explain the mechanisms of openness to the social world, which can be and sometimes are abused. A naturalistic framework does not dispute autonomy or rights, but it does point toward means of manipulation and toward areas in which further legal protection of rights and autonomous choice is needed. The author concludes by clarifying the ideal-typical degrees of coercion (indirect, direct and total) and compulsion (mild, severe and total) that serve the purpose of qualifying reduction of autonomy and responsibility in certain cases, and elaborating the middle-ground position between the “moral” and “brain disease” model of addiction.