Arsenic trioxide (As2O3) has a long history of use in medicine. However, it was almost forgotten in Western medicine in the recent centuries. Prompted by reports from China about successful treatment of acute promyelocytic leukemia (APL) with As2O3, there was again increasing interest in this drug in the 1990s. This review summarizes the considerable knowledge about the mechanisms of action of As2O3 that was gained during the last 5-10 years. It is focused in particular on the effects of As2O3 in non-APL cells. Since As2O3 seems to induce apoptosis and inhibits growth in a large variety of cellular targets, it might become an alternative or adjunct drug to conventional chemotherapy. As2O3 can even be effective in cells resistant to conventional cytostatic agents. Insight into the cellular mechanisms, in particular the impact of the redox state on sensitivity towards As2O3 opens the possibility to enhance As2O3 effects by appropriate combination therapies.