BACKGROUND: Melatonin (MLT) is known to possess potent antioxidant, antiproliferative, immune-modulating, and hormone-modulating properties. Clinical evidence suggests that MLT may have a possible role in the treatment of cancer. The authors systematically reviewed the effects of MLT in conjunction with chemotherapy, radiotherapy, supportive care, and palliative care on 1-year survival, complete response, partial response, stable disease, and chemotherapy-associated toxicities. METHODS: The authors searched 7 databases: MEDLINE (1966-February 2010), AMED (1985-February 2010), Alt HealthWatch (1995-February 2010), CINAHL (1982-February 2010), Nursing and Allied Health Collection: Basic (1985-February 2010), the Cochrane Database (2009), and the Chinese database CNKI (1979-February 2010). They included all trials that randomized patients to treatment, including MLT or a similar control group without MLT. RESULTS: The authors included data from 21 clinical trials, all of which dealt with solid tumors. The pooled relative risk (RR) for 1-year mortality was 0.63 (95% confidence interval [CI] = 0.53-0.74; P < .001). Improved effect was found for complete response, partial response, and stable disease with RRs of 2.33 (95% CI = 1.29-4.20), 1.90 (1.43-2.51), and 1.51 (1.08-2.12), respectively. In trials combining MLT with chemotherapy, adjuvant MLT decreased 1-year mortality (RR = 0.60; 95% CI = 0.54-0.67) and improved outcomes of complete response, partial response, and stable disease; pooled RRs were 2.53 (1.36-4.71), 1.70 (1.37-2.12), and 1.15 (1.00-1.33), respectively. In these studies, MLT also significantly reduced asthenia, leucopenia, nausea and vomiting, hypotension, and thrombocytopenia. CONCLUSION: MLT may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.