Cancer is a growing problem because it is a chronic disease that affects, not only patient health, but also its daily living. Concurrent cancer therapies have ameliorated cancer prevalence, but the severity and frequency of toxicity and side effects during therapy have led the scientific community to rediscover the possible therapeutic effectiveness of herbs and spices. Crocus sativus L., commonly known as saffron, has been used in folk medicine for centuries. Today, data from numerous in vivo and in vitro studies support its anti-cancer activity, making it a promising anti-cancer agent for study. In the present review, we focus on the anti-cancer activity of C. sativus and its derivates. Medications that are currently used as chemotherapeutic or anti-cancer agents are associated with side effects whether used at effective doses or at levels that exceed the therapeutic dose. Therefore, many cancer survivors suffer from serious and even life-threatening long- or short-term sequelae, so the development of alternative/coadjutant drugs is imperative.