Purpose: Cancer-related fatigue in adults has been the subject of considerable recent research, confirming its importance as a common and debilitating symptom, and establishing a number of evidence-based interventions. There has, however, been limited focus on the fatigue suffered by teenagers and young adults with cancer, a group recognized as having unique experiences and developmental needs. We have undertaken a systematic review of the literature to provide a comprehensive overview of studies evaluating fatigue in this younger patient group in order to guide clinical practice and future research. Method: We searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for literature containing data relating to any aspect of fatigue in patients aged 13-24 at cancer diagnosis or treatment. Results: Sixty articles were identified, of which five described interventional clinical trials. Cancer-related fatigue was consistently one of the most prevalent, severe, and distressing symptoms, and it persisted long-term in survivors. It was associated with a number of factors, including poor sleep, depression, and chemotherapy. There was little evidence for the effectiveness of any intervention, although exercise appears to be the most promising. Importantly, fatigue was itself a significant barrier to physical and social activities. Conclusion: Cancer-related fatigue is a major and disabling problem in young cancer patients. Effective management strategies are needed to avoid compounding the dependence and social isolation of this vulnerable patient group. Future research should focus on providing evidence for the effectiveness of interventions, of which activity promotion and management of concurrent symptoms are the most promising.