Anorexia nervosa (AN) is an eating disorder, mainly affecting women, with a lifetime prevalence of about 1%, that can run a chronic course. While an effective pharmacotherapy is lacking, it is hypothesized that the progesterone and type II glucocorticoid receptor antagonist mifepristone (RU486) might be useful, as it is well known that the hypothalamo-pituitary-adrenal axis (HPA) is activated in AN. Even if secondary to the eating disorder, an active HPA axis may contribute to maintaining the neuroendocrine, emotional and behavioral effects observed in AN. More specifically, it is suggested that the HPA axis interacts with limbic structures, including the insular and prefrontal cortices, to Uphold the changes in interoceptive and emotional awareness seen in AN. As such, it is proposed that mifepristone (RU486) reverses these effects by acting on these limbic regions. In conclusion, the theoretical efficacy of mifepristone (RU486) in improving symptoms of AN should be tested in randomized clinical trials. (C) 2016 Elsevier Inc All rights reserved.