This paper discusses the hypothesis that a 'drive for activity" in the presence of physiological and endocrine changes consistent with starvation is a characteristic symptom of acute anorexia nervosa (AN). This 'drive for movement', along with alertness and lack of fatigue, so unlike the motor slowing and loss of energy observed in simple starvation has been recognized in AN throughout history, but has received little attention in the past fifty years. Clinical reports and experimental evidence suggest that 'restlessness' and a 'drive for activity' vary in intensity, they appears to be starvation-dependent and to wane with food intake. Central nervous system (CNS) systems known to be involved in mediating activity and arousal levels that are altered by the negative energy expenditure in AN are reviewed. Among these, the corticotropin-releasing hormone (CRH) system, the melanocyte stimulating hormone/agouti-related protein (MSH/AGRP) system and the norepinephrine/epinephrine (NE/EPI) and dopamine (DA) system may contribute to the 'drive for activity' and alertness in AN. AN appears to represent a disorder of gene/environment interaction. Future research will reveal whether in individuals predisposed to AN, the 'drive for activity' reflects the reactivation of mechanisms important in food scarcity, controlled by one or more evolutionary conserved genes including those regulating foraging behavior. Recognition of the 'drive for activity' as a diagnostic symptom of AN and its assessment prior to re-nutrition would permit clarification of its role in the etiology of AN.