This chapter examines patterns of comorbidity between eating disorders and mood, anxiety, and substance use disorders along with evidence regarding support for different theoretical models that may account for these patterns. Although comorbidity estimates may be inflated by reliance on treatment-seeking samples and double counting of symptoms that overlap between syndromes, evidence supports elevated risk of mood, anxiety, and substance use disorders in anorexia nervosa, bulimia nervosa, and binge eating disorder. Data from family and twin studies support that eating and anxiety disorders may have a shared diathesis, consistent with the common cause model. Data from longitudinal studies suggest that eating disorders may increase vulnerability for developing a substance use disorder, consistent with the predisposition model. In contrast, comorbidity between eating and mood disorders, such as depression, remains poorly understood. Clinical issues regarding comorbidity of depression and eating disorders along with guidelines for clinicians treating patients with comorbid depression and eating disorders are discussed.