Life-threatening bleeding is frequent in acute leukemias, particularly in acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia, characterized by the balanced reciprocal translocation between chromosomes 15 and 17. Laboratory assessments show profound hemostatic imbalance compatible with the clinical picture of disseminated intravascular coagulation. Activation of the coagulation system, hyperfibrinolysis and nonspecific proteases activity can be observed in this condition. An important pathogenetic role is attributed to the leukemic cell properties for activating hemostatic mechanisms. This review will summarize what is currently known about the coagulopathy of APL, the principal pathogenetic mechanisms, and the therapeutic tools for the management of this complication. Special attention will be devoted to the new therapy with all-trans retinoic acid, which has completely changed the natural history of APL and APL-related coagulopathy.