With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide, acute promyelocytic leukemia (APL) has become a highly curable malignancy. Approximately 90% of patients achieve complete remission with induction, which generally includes ATRA and an anthracycline-based chemotherapy. Early death, either before treatment is initiated or during induction, has emerged as one of the most critical issues involved in the current care of patients with APL. The main cause of early death in APL is bleeding, often intracranial. It has become increasingly clear that induction therapy should be initiated in patients at the earliest time possible, even before confirmation of the diagnosis of APL has been made. In this roundtable, several experts discuss important insights into the high rate of early death observed in APL. In addition to the importance of rapid diagnosis, the pathophysiology of the coagulopathy associated with APL will be discussed, as will factors that may be predictive of early death and potential interventions to prevent this important limitation to the cure of many, if not most, patients.