Fatigue, experienced by patients during and following cancer treatment, is a significant clinical problem. It is a prevalent and distressing symptom yet pharmacological interventions are used little and confer limited benefit for patients. However, many cancer patients use some form of complementary and alternative medicine (CAM), and some evidence suggests it may relieve fatigue. A systematic review was conducted to appraise the effectiveness of CAM interventions in ameliorating cancer-related fatigue. Systematic searches of biomedical, nursing, and specialist CAM databases were conducted, including Medline, Embase, and AMED. Included papers described interventions classified as CAM by the National Centre of Complementary and Alternative Medicine and evaluated through randomized controlled trial (RCT) or quasi-experimental design. Twenty studies were eligible for the review, of which 15 were RCTs. Forms of CAM interventions examined included acupuncture, massage, yoga, and relaxation training. The review identified some limited evidence suggesting hypnosis and ginseng may prevent rises in cancer-related fatigue in people undergoing treatment for cancer and acupuncture and that biofield healing may reduce cancer-related fatigue following cancer treatments. Evidence to date suggests that multivitamins are ineffective at reducing cancer-related fatigue. However, trials incorporated within the review varied greatly in quality; most were methodologically weak and at high risk of bias. Consequently, there is currently insufficient evidence to conclude with certainty the effectiveness or otherwise of CAM in reducing cancer-related fatigue. The design and methods employed in future trials of CAM should be more rigorous; increasing the strength of evidence should be a priority.