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. 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. 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. 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.