The optimal dose and efficacy of ¹³¹I treatment of children and adolescents with well-differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic challenge is to achieve the maximum benefit of ¹³¹I to decrease disease-related morbidity and obtain disease-free survival while avoiding the potential complications of ¹³¹I therapy. We systematically reviewed the published literature on children and adolescents with WDTC and pulmonary metastases treated with ¹³¹I to examine outcomes after ¹³¹I administration and the risks and benefits of therapy. After reviewing 14 published articles, 9 articles met our inclusion criteria encompassing 112 pediatric and adolescent patients with WDTC and pulmonary metastases 21 years of age or younger at diagnosis spanning a follow-up period of 0.6–45 years. ¹³¹I therapy after surgery and thyrotropin suppression resulted in complete, partial, and no disease response in 47.32%, 38.39%, and 14.29% of patients, respectively. Five studies provided data on disease response in relation to ¹³¹I dose. In general, nonresponders received the highest ¹³¹I doses and complete responders received a higher dose than partial responders. The disease-specific mortality rate was 2.68%. Survival was 97.32%. A second primary malignancy occurred in one patient. One out of 11 patients studied experienced radiation fibrosis. This review confirms that the majority of pediatric and adolescent patients with WDTC and pulmonary metastases treated with ¹³¹I do not achieve complete response to therapy, yet disease-specific morbidity and mortality appear to remain low. It is therefore prudent to use caution in the repeated administration of ¹³¹I to such patients to ensure that adverse effects of therapy do not cause more harm than good in a disease that has an overall favorable natural course. Long-term prospective studies are needed to analyze disease-specific morbidity and mortality, recurrence rate, dose-specific response, and dose-related adverse effects of ¹³¹I in this patient population.