The incidence of bleeding in patients with acute leukemia varies widely based on several factors, including the specific type of leukemia, the stage of the disease, the patient’s comorbidity, and the presence and severity of thrombocytopenia. Thrombocytopenia due to both bone marrow infiltration and chemotherapy; disseminated intravascular coagulation (DIC) (more common in patients with acute promyelocytic leukemia, APL); impaired platelet function; hypofibrinogenemia due to the consumption of fibrinogen during systemic activation of coagulation or impaired synthesis by asparaginase may alone or in combination variably influence the risk of bleeding. About 30–50% of patients will experience bleeding, which in about half of cases can be severe, with intracranial hemorrhage occurring in 3–6% of cases. Prevention and management of bleeding is mainly based on the use of platelet transfusions with a minimal target of 10 × 109/L platelets or higher in patients with active bleeding, DIC, or APL, and the management of coagulopathy with replacement of fibrinogen. The prophylactic use of antifibrinolytic agents is not recommended due to the lack of efficacy, while it can be of benefit in selected situations (e.g., oral mucosal bleeding).