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Medical problems that arise due to severe restricting and/or purging may be misdiagnosed or suboptimally treated, from outpatient clinics to top medical hospitals. A symptom may be presumed to be a psychological manifestation of the eating disorder and inappropriately dismissed for further medical evaluation. Alternatively, a detailed medical workup may be performed, overlooking a classic relationship between starvation and a physical finding, which delays referral to eating disorder care. This review article focuses on rare medical issues (also called “zebras” in medical training), diagnoses that may be missed in patients with eating disorders, and best practices for management, organized by organ system.A PubMed search was performed, using search terms “eating disorder,” “anorexia nervosa,” and “bulimia nervosa” in combination with different words for each organ system and known medical manifestations of severe eating disorders, with high quality and relevant studies from the past 20 years cited.Adults with eating disorders may present with extreme organ dysfunction and atypical signs and symptoms of typical medical problems. Timely diagnosis, risk awareness, appropriate treatment, and avoidance of harm are all vital. With judicious management and nutritional rehabilitation, most of these complications will significantly improve or resolve. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:331–344).