BACKGROUND: Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population. METHODS: Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded. RESULTS: A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium. CONCLUSIONS: The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.