OBJECTIVES: To discuss the symptoms of fatigue, sleep disturbance, and pain in children undergoing cancer treatment, and a framework for the clustering of these symptoms. DATA SOURCES: Published articles, research studies, and clinical experience. CONCLUSION: Symptoms experienced by children undergoing cancer treatment are distressing, prevalent, and rarely occur in isolation. Multiple symptoms may share underlying mechanisms, influence the severity of the distress experienced, and interfere with a child’s ongoing development. Developing knowledge of the relationships among symptoms may be important for improving quality of life during cancer treatment while supporting the child’s development. IMPLICATIONS FOR NURSING PRACTICE: Nurses must be aware of the symptom distress occuring in children with cancer to manage its symptoms and its treatments.