The properties of arsenic trioxide (arsenic) have been known for centuries. This compound has been used, among others, in the industrial production of paints and glass and also for the conservation of leather and wood. Although arsenic trioxide is highly toxic, this compound was shown to have a therapeutic potential as early as the fifteenth century. The period between the seventeenth and nineteenth centuries resulted in the development of new arsenic-based drugs which were applied for the treatment of skin diseases and acute promyelocytic leukemia. The mechanism of action of arsenic trioxide is mainly related to the induction of apoptosis (programmed cell death) in cancer cells. In particular it involves effects on the activities of JNK kinases, NF-kB transcription factor, glutathione, caspases, as well as pro- and anti-apoptotic proteins. Experiments investigating the effect of arsenic trioxide on cell lines such as glioma and prostate, breast, stomach, liver, and ovarian cancer are in progress. There are also clinical trials underway aimed at the use of arsenic trioxide with ascorbic acid, retinoid acid, and growth factors in combined therapy.