Melatonin is a molecule with numerous properties, which are applicable to the treatment of different types of cancers. Experimental in vitro and in vivo studies conducted with human cancer cells or animal models of carcinogenesis, have shown that melatonin enhances apoptosis and inhibits cell proliferation of several human cancer cells, reduces tumor growth rate and its metastases, reduces the side effects of chemotherapy and radiotherapy, decreases the resistance to standard cancer treatments, and potentiates the therapeutic effects of other conventional therapies. These satisfactory results obtained from “bench” need to be studied in clinical trials to verify whether they are applicable to “bedside”. In this article we review the clinical trials carried out in the last 25 years which are focused on the therapeutic use of melatonin in cancer treatment. We conclude that melatonin is an effective adjuvant drug to practically any conventional cancer therapy since it is capable of improving the quality of life of patients, by normalizing sleep and alleviating general symptoms associated with tumor disease and treatment such as pain, asthenia, anorexia, etc. In the particular case of hormone-dependent breast cancer, melatonin's antiestrogenic properties make this indoleamine ideally suited for use in association with other synthetic anti-estrogen agents, as melatonin increases their efficacy while reducing their undesirable effects. Furthermore, melatonin could be an appropriate co-treatment for preventive treatment of breast cancer in people with elevated risk for this kind of neoplasia.