In women with premature ovarian insufficiency (POI), hormonal therapy (HT) is indicated to decrease the risk of morbidity and to treat symptoms related to prolonged hypoestrogenism. While general recommendations for the management of HT in adults with POI have been published, no systematic suggestions focused on girls, adolescents and young women with POI following gonadotoxic treatments (chemotherapy, radiotherapy, stem cell transplantation) administered for pediatric cancer are available. In order to highlight the challenging issues specifically involving this cohort of patients and to provide clinicians with the proposal of practical therapeutic protocol, we revised the available literature in the light of the shared experience of a multidisciplinary team of pediatric oncologists, gynecologists and endocrinologists. We hereby present the proposals of a practical scheme to induce puberty in prepubertal girls and a decisional algorithm that should guide the clinician in approaching HT in post-pubertal adolescents and young women with iatrogenic POI.