Abstract Radiation therapy represents an important approach in the therapeutic management of children and adolescents with malignant tumors and its application with modern techniques – including Proton Beam Therapy (PBT) – is of great interest. In particular, potential radiation-induced injuries and secondary malignancies – also associated to the prolonged life expectancy of patients – are still questions of concern that increase the debate on the usefulness of PBT in pediatric treatments. This paper presents a literary review of current applications of PBT in non-Central Nervous System pediatric tumors (such as retinoblastoma, Hodgkin Lymphoma, Wilms tumor, bone and soft tissues sarcomas). We specifically reported clinical results achieved with PBT and dosimetric comparisons between PBT and the most common photon-therapy techniques. The analysis emphasizes that PBT minimizes radiation doses to healthy growing organs, suggesting for reduced risks of late side-effects and radiation-induced secondary malignancies. Extended follow up and confirms by prospective clinical trials should support the effectiveness and long-term tolerance of PBT in the considered setting.