The concepts of self-regulation and autonomy are examined within an organizationalframework. We begin by retracing the historical origins of the organizational viewpoint in earlydebates within the field of biology between vitalists and reductionists, from which the constructof self-regulation emerged. We then consider human autonomy as an evolved behavioral,developmental, and experiential phenomenon that operates at both neurobiological andpsychological levels and requires very specific supports within higher order social organizations.We contrast autonomy or true self-regulation with controlling regulation (a nonautonomous formof intentional behavior) in phenomenological and functional terms, and we relate the forms ofregulation to the developmental processes of intrinsic motivation and internalization.Subsequently, we describe how self-regulation versus control may be characterized by distinctneurobiological underpinnings, and we speculate about some of the adaptive advantages that mayunderlie the evolution of autonomy. Throughout, we argue that disturbances of autonomy, whichhave both biological and psychological etiologies, are central to many forms of psychopathologyand social alienation.