Recent advances in treatment for pediatric cancers has increased overall survival rates. As more and more survive pediatric cancer, we continue to see the emergence of late effects of treatment within pediatric and the growing adult survivor population. The evaluation of late effects was initiated approximately two decades ago, and has become an extremely important facet of pediatric oncology. This review delves into several of the most serious organ-specific late effects of pediatric cancer treatment, outline what we know and what we do not currently understand about preventing or reducing them. Clinical and bench research are necessary to develop interventions that will avoid or mitigate late effects and improve the health of pediatric cancer survivors.