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Fatigue is a common symptom found in the adult oncology literature. However, little is known about its occurrence, causes, conceptual and operational definitions, and effective interventions in children and adolescents with cancer.The purpose of this study was to define and describe fatigue experienced by children and adolescents receiving treatment for cancer. A focus group approach was used to reveal the contextual understanding of fatigue through discussions. Eleven focus groups were convened during a 2-month period at two major children's cancer centers. Twenty-nine children participated in the focus groups: 14 were 7 to 12 years of age and 15 were 13 to 16 years of age. Focus groups were held separately for each age group, lasted from 30 to 45 minutes, and were audiotaped. The audiotapes were transcribed verbatim, and Ethnograph software was used to number the data to sort and code the information. Researchers at both study sites coded the data independently within the context of the unit of analyses, which, in this study, were the study questions. Codes and descriptions were developed for the definitions of fatigue, causes of fatigue, and what helps. Eight codes emerged from the children groups and 12 from the adolescent groups to define fatigue. Six codes were developed from the children groups and 12 from the adolescent groups to describe causes of fatigue. Three codes from the children groups and eight from the adolescent groups described what helps. This study is the first to evaluate fatigue as a symptom in children and adolescents with cancer. Findings from this study will provide the foundation for developing a conceptual model for cancer-related fatigue in children and adolescents.