In addition to choosing a state-of-the-art regimen including all-transretinoic and anthracycline chemotherapy, modern management of acute promyelocytic leukemia (APL) implies the adoption of appropriate supportive measures, rapid establishment of an accurate genetic diagnosis, correct assessment of response to therapy and evaluation of the risk of disease recurrence by molecular monitoring. However, the general consensus about this overall strategy for APL treatment still leaves room for a number of controversial issues. In the present article, we review the current standard practice and controversial issues in the treatment of patients with newly diagnosed APL, including the management of special situations such as elderly patients, children and pregnant women.