Fatigue is a prevalent and distressing symptom in people with cancer, and adolescents with cancer are no exception. Research on fatigue in the context of age and development will help in the development of age-specific prevention and management guidelines. The developmental profile, cancer epidemiology, and research needs related to adolescents with cancer are unique. A number of descriptive studies now form the foundation of scientific knowledge about cancer-related fatigue in adolescents. From this research, a definition of fatigue has been constructed and age-specific instruments have been developed. In addition, several correlates and interventions have been proposed for future testing. This article reviews relevant literature related to the symptom of fatigue in adolescents with cancer, discusses future research directions, and recommends clinical strategies for management of fatigue in this population.