Arsenic Trioxide is an old drug that has recently re- introduced into new medicine. It is very potent against a specific type of leukemic cells harboring translocation between chromosomes 15 and 17. It has been demonstrated that this drug is effective against all stages of acute promyelocytic leukemia, including for remission induction of relapsed cases, or as first-line treatment. It is also useful in the consolidation/maintenance phase of treatment. Many trials are ongoing to determine the best and optimum schedule for this drug as a single agent or in combination with other drugs. In the future, its indications might extend to other malignancies. In this review, we will study biologic effects of arsenic trioxide on APL cells and the results of clinical trials on the treatment of APL. We will also discuss the toxicity and minimal residual detection during patient follow-up.