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The goal of this study was to investigate the variables that best predict functional impairment in children and adolescents. Two hundred and eight psychiatric and 129 pediatric children aged 7 to 17 years were assessed with measures of psychopathology, functional impairment, temperament, marital discord, educational style, coping, developmental milestones, stressful life events, medical history, school information, and family history of psychopathology. Multiple regression models adjusted by psychopathology were estimated. The global model, which included all the significant variables in partial models, revealed the following predictors of impairment: receiving review lessons, chronic disease or handicap, the presence of problems the child interpreted as stressful, late onset and long duration of psychopathological problems. These indicators could be useful for the proper identification of children with severe difficulties, in order to provide them with adequate psychological services.