Over the last 4 decades, there has been a tremendous improvement in survival of children diagnosed with cancer, with 5-year survival rates now averaging 80%. The rapidly growing population of childhood cancer survivors creates an obligation to understand the health and well being of these individuals. Use of cancer therapy at an early age can produce a large burden of morbidity, as demonstrated quite conclusively by the fact that approximately two thirds of these survivors will experience at least one late effect, and approximately one third will experience a late effect, that is, severe or life threatening. Long-term complications in childhood cancer survivors, such as impairment in growth and development, neurocognitive dysfunction, cardiopulmonary compromise, endocrine dysfunction, renal impairment, gastrointestinal dysfunction, musculoskeletal sequelae, and second cancers, are related not only to the specific therapy used, but may also be determined by individual host characteristics. This review provides an update of the known late effects observed in childhood cancer survivors to provide the rationale for evaluation of specific long-term problems in this growing population of individuals at risk for chronic health conditions.