Psychotropic polypharmacy (PP) is defined as the practice of prescribing two or more medications for one or more diagnosed psychiatric disorders. Data on the rates of PP in pediatric population demonstrate that this practice is on the rise. The evidence base on the efficacy of psychotropic polypharmacy in pediatric psychiatric practice is limited. Due to the complexity of the etiology and severity of mental disorders in children, the use of PP is sometimes unavoidable. In such cases, each combination of drugs used must have its etiological and clinical justification because only then will PP be useful and justified, and not excessive and burdened with side effects. This review brings the main findings in this area with a clear conclusion that more high quality and longitudinal studies are needed to answer the questions of the effectiveness and safety of psychotropic polypharmacy in the treatment of mental disorders in children and adolescents. Until then, the attitude to combination pharmacotherapy should be conservative, and combining psychotropic medications should be closely monitored due to the specific concern of the risks of the increase of adverse events with polypharmacy.