Long-term survivors of childhood and adolescent cancer are a high-risk population of patients who often seek acute or preventive health care with a primary care clinician. Of importance is that the curative therapy administered for the cancer also affects growing and developing organ systems. Following chemotherapy, radiotherapy, and surgery, many survivors will experience chronic or late-occurring health problems, often not becoming clinically apparent until decades after therapy. Survivors face an increase in risk of serious morbidity, premature mortality, and diminished health status associated with their previous cancer therapy. Risk is further modified by the survivor's genetics, lifestyle habits, and comorbid health conditions. The aims of this review are threefold: (1) to provide an overview of the risks faced by long-term survivors of pediatric cancer; (2) to highlight the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, and encourage use of these guidelines when following long-term survivors; and (3) to provide a brief overview of key late effects of childhood cancer therapy. © 2009 Elsevier Inc. All rights reserved.