Because of therapeutic advances over the past 50 years, long-term survival is now a reality for nearly 80% of children and adolescents diagnosed with cancer. The growing population of childhood cancer survivors is notable for its vulnerability to adverse health outcomes, many of which may not become clinically apparent until years after therapy completion. Early detection, prevention, and ameliorative interventions provide the opportunity to reduce cancer-related morbidity and mortality. This review is intended to complement the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. The objective of this review is to familiarize readers with the diverse health risks experienced by childhood cancer survivors that stem from the heterogeneous therapeutic interventions required to achieve disease control.