Objective: Many patients with anorexia nervosa develop an intractable and debilitating illness course. Our aims were to (i) conduct a systematic review of randomised controlled trials (RCTs) of treatment for chronic anorexia nervosa participants, and (ii) identify research informing novel therapeutic approaches for this group. Methods: Systematic search (SCOPUS plus previous reviews date 2011) of literature for (i) RCTs of treatment that included anorexia nervosa participants with a mean duration of illness of at least 3 years, (ii) studies reporting new treatments addressing factors associated with chronicity. Results: Evidence of efficacy for treatment approaches in severe and enduring anorexia nervosa is limited. Only one unpublished RCT designed to test a specific psychological approach for these patients was identified. There is a probable advantage for specialist psychotherapy over treatment as usual, and a promising study of relapse prevention with cognitive behaviour therapy (CBT) for anorexia nervosa (CBT-AN). Open trials have, however, reported developments in psychological therapies that warrant further specific evaluation. These include forms of CBT modified for anorexia nervosa, cognitive remediation therapy with emotion skills training, the Maudsley Model for Treatment of Adults with Anorexia Nervosa, the Community Outreach Partnership Program, Specialist Supportive Clinical Management and the approach of Strober with its emphasis on therapeutic alliance and flexible goals. Conclusions: Treatment trials need to move beyond targeting core eating disorder pathology (primarily weight restoration) and examine efficacy and effectiveness in minimising harm and reducing personal and social costs of chronic illness. There is also a need to develop better definitions of chronicity, with or without treatment 'resistance' specifiers.