Objective: To compare family health and characteristics in children with chronic fatigue syndrome (CFS), in juvenile rheumatoid arthritis (JRA), and emotional disorders. Method: Parents of 28 children and adolescents aged 11 to 18 years with CFS, 30 with JRA, and 27 with emotional disorders (i.e., anxiety and/or depressive disorders) were recruited from specialty clinical settings and completed interviews and questionnaires assessing family health problems, parental mental distress, illness attitudes, and family burden of illness. Results: Parents of children with CFS were significantly more likely than those of children with JRA to report a history of CFS-like illness, high levels of mental distress, and a tendency to experience functional impairment in response to physical symptoms. Families of children with CFS were characterized by significantly greater emotional involvement and reported greater family burden related to the child's illness in comparison with families of children with JRA. Conclusions: CFS in childhood and adolescence is associated with higher levels of parental CFS-like illness, mental distress, emotional involvement, and family illness burden than those observed in association with JRA, a chronic pediatric physical illness. J. Am. Acad. Child Adolesc. Psychiatry, 2005;44(2):150-158. Key Words: chronic fatigue syndrome, family health, family characteristics.